An amalgam of clinical diseases caused by a variety of fungi which often lead to subcutaneous cyst formation at the site of traumatic implantation of the fungus in immunocompetent patients.

Phaeohyphomycetes: broad definition, fungi that produce brown-black structures at least at some period in life cycle, particularly spores (includes only chaetothyriales and dothedales). Restricted definition, fungi that are vegetatively melanized throughout their life cycle (includes only chaetothyriales).

Subcutaneous forms often progress from chronic to systemic infections. Infections tend to be chronic and localized in hosts and spread rapidly in immunocompromised patients. Initial lesion is cystic (forms sac filled with fluid) followed by necrosis. Disease expands via satellite colonies.


Fungus in tissue samples appears as yeast-like cells and /or hyphae, but never as sclerotic bodies. The only exception is E. dermatitidis, which occasionally produces sclerotic bodies (isotropically enlarged cells with one septum), also called muriform bodies, and multicellular/planate forms.


Patient presents with solitary, discrete, well encapsulated nodule or cyst closed sac with distinct membranes 9which becomes infiltrated with pus-like fluids and fungus) in dermis or muscle

Lesions may occur all over body

Patient often remembers trauma since cyst develops shortly after infection

Nodule usually becomes elevated

Central area becomes necrotic and becomes an encapsulated abscess (cyst)

Necrotic area fills with yellowish, viscous, purulent fluid which, when aspirated, exhibits fungal elements.

Identification requires culture.


Septa are structures that separate cells within a hypha. Fungi are often characterized by the type of septation pattern they exhibit.

Complete septa are walls that have no pores. These are usually found between the vegetative and reproductive or specialized cells of a fungus (such as gametangia) to ensure that the two regions are kept distinct.

Micropore septa are walls which have very small pores between adjacent cells. This allows cells to communicate with neighboring cells also allows nuclear migration (the movement of a nucleus form one cell to another). Since micropore septa allow the cytoplasm of two cells to mix, there is debate as to whether or not these fungi are continuous.

Aseptate is a term used to describe fungi that lack septa except to wall off their reproductive cells (with complete septa). Since nothing separates one cell from another, these fungi are often called coenocytes, meaning that they are multinucleate. Aseptate fungi include the Oomycota and the Chytridiomycota.

Regularly septate is a term used to describe fungi that have septa at regular intervals. These fungi include the Ascomycota, Basidiomycota and Fungi Imperfecti.

Irregularly septate is a term that is used to describe fungi which have septa at random positions. Irregularly septate fungi include the Zygomycota.


Looking at the gross compartmentalization of a fungus may give clues about the fungus under study.

Fungal-like protists and the Chytridiomycota tend be aseptate, except to delimit reproductive or specialized cells (such as sporangia and gametangia). Since they are multinucleate, they are often call coencytes.

The Zygomycota tend to be aseptate or have septa formed at irregular intervals in their hyphae. (Complete septa may also form to wall of specialized regions.)

It has been observed that as these fungi age, they begin to form septa and compartmentalize. This is thought to be due to the fact that as the mycelium gets bigger, toxins accumulate in the older regions (where nutrients are first depleted). Septa are required to prevent toxins from diffusing into the hyphal tips (apical ends), which have access to more nutrients and are where most growth occurs.

Ascomycota and Basidiomycota are regularly septate and tend to form complete septa or micropore septa between mother and daughter cells.

Ascomycota tend to form hyphal septa at regular intervals. The septa are "simple septa" with a central pore and Woronin bodies. Woronin bodies are organelles with their own DNA that are found only in ascomycetes and have no known function.

Basidiomycota tend to form hyphal septa at regular intervals. The septa are "dolipore" types of septa with parenthesome membranes or "pulley wheel" types of septa with pulley wheel plugs with a central pore. The central pore allows for communication between cells. Parenthesomes are membrane complexes with a role in communication.

Simple Septum Dolipore Septum Multi-pore Septum PulleyWheel Septum





Simple Septum Formation







Basidiomycetes form clamps in order to perpetuate the dikaryotic condition in hyphae. Clamp formation is unique to Basidiomycota. This mechanism is designed to keep nuclei paired until conditions are right for mating.
















Hyphal tips are extended by apical extension. Apical vesicles bind to the apical end of a hyphal tip and extend the hyphae. Extension works by packaging the enzymes necessary for cell wall growth in vesicles and allowing those vesicles to fuse with (and thereby extend) the cell wall.

Hyphal Oomycota exhibit random dispersion of apical vesicles

Hyphal Zygomycota have a high concentration of apical vesicles at the tip

Hyphal Ascomycota, Basidiomycota, and Fungi Imperfecti develop structures called spitzenkarpers at their growing hyphal tips.

The spitzenkarper is present in cells only when they are actively growing. Though the spitzenkarper may appear to be a single structure at first, under higher magnification it is clear that the spitzenkarper is actually a mass of microvesicles concentrated among macrovesicles. It is a massive system of vesicle-mediated exocytosis used to construct a cell wall during extension of hyphal tip or bud enlargement. It works by packing the enzymes necessary for digestion into vesicles which are then exocytosed and released into the media where they break down complex macromolecules into units which can be absorbed by the fungus. These nutrients are used as fuel for the fungus and help it grow at a maximal rate. Vesicles may also contain components of the cell wall.


clinical history that suggests fungal infection (usually provided by the patient)

observation of fungus in clinical specimens

the fungus observed must be compatible with the disease reported

adequate evidence must be provided that the causative agent is actually a fungus that was properly identified


There is a general lack of government reporting requirements as far as funagal infection is concerned, though the CDC strongly suggests reporting any incidences of histoplasmosis and coccidiodomycosis.

It is relatively difficult to document cases of fungal infection since symptoms can easily be confused for symptoms of the flu or heart disease.

Fungal diseases are generally not communicable, so they are not a real threat to public health.

The exact mycosis or the relevance of mycosis may be difficult to establish, especially in patients who are immunocompromised due cancer or other degenerative diseases and may have illnesses other than fungal infection.

Some organisms (such as P. carinii, which was once thought to be a protozoan) have only recently been defined as fungi.

Mycoses have recently been given special attention since compromised patients who develop mycoses (especially infections by Candida and Aspergillus species) have a very high mortality rate. For this and other reasons, mycoses are more likely to be reported nowadays. However, fungi are probably not becoming more virulent, though a few are starting to develop antifungal resistance. The increase in the number of cases of mycosis can be attributed to two developments:

There is increased awareness of fungal infection and as a result more professionals get mycological training.

Beginning with the advent of antibiotics, people have been living longer. As a result, more people reach the age at which their immune systems begin to fail and they become compromised and are at risk for fungal infection. The AIDS epidemic has also contributed to the increase in number of immunosuppressed hosts.


· Factors that predispose humans to fungal infections generally compromise the host’s immune system such that the host cannot resist a fungal infection as a healthy person would. Such factors include prolonged antibiotic therapy, underlying disease (such as HIV, cancer, diabetes, etc.), age, immunosuppressive drugs, irradiation therapy, and burns.

· Other factors that predispose us to mycosis allow fungi to bypass the skin and mucous barriers that generally protect us, invade our systemic circulation, and access areas than microbes would otherwise never be able to colonize. These factors include surgical procedures iatrogenic dialysis, drug abuse using needles, burns and transplants.

· People who travel may also be exposed to strains of fungi in doses their bodies may not be able to handle.

Early diagnosis of invasive fungal infections is necessary for proper treatment and may decrease the high mortality rate associated with serious systemic mycoses. In many cases, however, there are obstacles to early diagnosis:

In immunocompromised patients, typical signs and symptoms of fungal infection are frequently absent.

Few clinical features are unique to fungal infection so many cases may be misdiagnosed.

Even when assay for the presence of fungi, sputum and blood cultures may give false positive results

Invasive procedures are sometimes necessary to diagnose fungal infection, but these procedures are often contraindicated in immunocompromised hosts.


Pathogenic fungi can be classified as primary pathogens or secondary pathogens based on their virulence.

Primary pathogenic fungi are fungi that are free-living fungi which are commonly pathogenic in normal hosts and severely pathogenic in compromised hosts

Secondary pathogenic fungi differ from primary pathogenic fungi in that they can be either free-ling, exosymbionts, or endosymbionts and are pathogenic only in compromised hosts. For example, dermatophytes (fungi which live on our skin) may enter the body of an immunocompromised host through a cut and cause and systemic fungal infection. Secondary pathogenic fungi do not pose a threat to persons with a healthy immune system ands are opportunistic.


In order to successfully infect a host, a fungus (or any other microbial pathogen) must accomplish four things:

gain entry to the interior of the body

This can be through the lungs or other orifices, through traumatic implantation (in which case fungus gets introduced into tissues and establishes lesions), or by surface colonizers (such as Candida albicans) invading deeper tissues to produce a systemic infections.

multiply and grow within the host until there are sufficient numbers of the fungi to threaten the host and illicit symptoms of infection

resist (or at least not stimulate) host defenses and evade immunological mechanisms

live using the host as a source of nutrition

This can result in necrosis (tissue death) and/or tissue irritation (rashes, granulomas, etc.) Granulomas (structures that arise when the host tries to "wall off" the pathogen) are significant in that they are signs that the host has recognized and is trying the limit the infection.


In order to be effective pathogens, fungi must be well adapted to the conditions within a human host.

Pathogenic fungi must be able to grow at elevated temperatures, (usually between 35 – 40*C). Any fungus that can grow near this range is a potential pathogen. Dermatophytes (which live on the skin where it is slightly cooler) must be able to live near 33*C

They must be able to grow at the reduced redox potentials characteristic of human hosts

As already discussed, they must be able to avoid cell-mediated and innate immunity of hosts. Our immune systems have evolved to withstand the vast majority of fungal infections, so most fungi do not pose a threat.


Virulence factors are mechanisms and/or structures that fungi (in fact, all microbes) have developed that give them an advantage as pathogens. Virulence factors are particularly interesting to mycologists because they provide clues about how fungi survive within their hosts. This information can be used to design new drugs and antifungal agents to fight infections. Fungal pathogens are generally difficult to treat because (unlike bacteria) they are eukaryotic, which means that they use many of the same pathways as our own cells do.

To identify virulence factors a mycologist might knock out certain genes to determine their role in virulence. In mouse models, for example, when the gene encoding melanin in the cell wall of Cryptococcus neoformans was knocked-out, the fungus became less virulent, which indicated that melanin might play some role in virulence. Similar findings were made when the capsule of C. neoformans was studied.

Miscellaneous virulence factors:

Dimorphism / Polymorphism

· Dimorphism refers to the ability of fungi to grow as two or more forms (i.e. molds and yeasts). A fungus may assume either the yeast or mold form under different growth conditions. In hosts, fungi generally grow as yeasts. It has been postulated that this may confer an advantage to the fungus since in the yeast form the fungus may able to reproduce asexually (by budding) faster than the mold form might and, therefore, might be able to spread through the host’s system more rapidly. Dimorphism is difficult to prove as virulence factor because it is difficult to say with certainty that growing with a different morphology conveys an advantage.

· In the case of Candidia albicans, which is a pleomorphic fungus that is commonly found on the skin, it is hypothesized that the fungus may have evolved as man did and that multiple morphisms reflect changes in symbiosis.

· Note: Some fungi are isotropic, meaning that rather than take on a new from in the host, they grow larger to avoid phagocytosis by host immune cells.

Capsules (See C. neoformans above)

Cell walls

Fungal cell walls are composed of beta-glucans, chitin, chitosan, melanin, and mannoprotein which may act as virulence factors. (The chitin and beta-glucan aggregate to form microfibrils.) Certain surface antigens and surface hydrophobicity may also play a role in the virulence of certain fungal species, such as Candida albicans.

Siderophores & Fe3+ Reductases

These are organic Fe3+ chelating substances used to collect iron in the host.

Unique membranes

Fungal plasma membranes contain ergosterol rather than cholesterol.



Innate immunity refers to the natural defenses a host has against fungal infection upon first exposure to the fungus. The innate immunity is nonspecific and is effective against infection by most microbes. The natural immunity of humans to fungal infection is high, meaning that we are generally very efficient at launching a successful immune response against any fungi we might contact. Natural immunity involves innate defenses:

physical barriers, such as skin and mucous membranes

chemical barriers, such as secretions and serum factors

the body’s natural effector cells, which may or may not be phagocytic


There are two:

Those that allow the fungus to enter the host and cause disease

Those of the host that either limit the growth or the survival of the fungus within host tissues


There are three factors that determine the outcome of any fungal infection and whether or not the host develops resistance:

The size of the inoculum. Infection often only depends upon exposure to a sufficient inoculum size (particularly for pulmonary inocula and for traumatic implantation of the inoculum into tissue) for primary infections. Endemic areas are regions where spores can be found in large numbers and have a high incidence of fungal infection.

The general resistance of the host. The lower host defenses are, the more likely it is that the host will be susceptible to fungal attack and the more severe the outcome. Lower resistance implies that a smaller inoculum is required to develop an infection.

The inherent virulence of the fungus. Obviously, the more virulent the fungus, the harder it is for the host to fight infection and the more severe the illness.

Basically then, those most at risk for serious mycosis are compromised hosts exposed to a large inoculum of a virulent fungus.


Thus, for primary pulmonary infections, infection is usually associated with an endemic area (and/or infected hazardous site) and with the inhalation of a large number of infecting propagules (spores). As one would expect, the fungi with the highest virulence are the ones commonly responsible for primary infections associated with spore inhalation: Histoplasmosis, Blastomycosis, Paracoccidiodomycosis, and Coccidiodomycosis. Recovery from both histoplasmosis and coccidiodomycosis induces protective resistance (specific immunity). (Specific immunity to fungal infections has been shown to wane with age.

Normal patients exposed to such fungi generally fight off infection easily with no sign of illness (asymptomatic). However, if exposed to a large enough inoculum of virulent fungus, a person with an intact immune system may develop a chronic infection. The chronic infection may require treatment such as antifungal drugs, surgery, and require the patient to abstain form smoking. A compromised patient may easily develop systemic and progressive illness depending on the specifics surrounding the infection.


These infections are usually initiated as pulmonary infections in immunocompromised hosts and are generally not associated with endemic areas. Host defenses are important for resistance to fungal infections. The sub-optimal state of the host allows low doses of inoculum to cause disease (e.g. Aspergillosis).

These mycoses include: Aspergillosis, Candidiasis, Zygomycosis, and Cryptococcosis. Generally, the fungi of these mycoses are thought to be less virulent that those of the primary endemic mycoses. Recovery from these infections is not associated with the development of specific immunity against the fungus responsible.

Farmer’s Lung is a disease that was common among farmers who worked with moldy hay and were thereby exposed to a high number of Aspergillous conidia. Treatment ofter required surgical resectioning of the lung.

Pigeon Breeder’s Disease is a disease that was common among pigeon breeders who developed chronic pulmonary cryptococcosis.


Granulocytes (named for the granules found within their cytoplasm) include neutrophils (PMNs), eosinophils, and basophils. All have lobed nuclei. PMNS are th only granulocytes which are phagocytic. They circulate in the blood and tissues and the are the first phagocytes to arrive at the site of inflammation. Neutropenia is the condition of having a low number of PMNs and predisposes a person to Aspergillosis and candidiasis. Conidia are small and can be easily phagocytosed, but once spores begin to germinate they may grow too big for phagocytosis.

The mononuclear phagocytes include monocytes (which circulate in the bloodstream) and macrophages (which migrate into tissues). They are the second type of phagocyte to arrive at the site of inflammation. Monocytes actually differentiate into macrophages.

Macrophages also

release CKs that stimulate specific immune responses

are APC

are part of the RE system

are less efficient killer than PMNs, except when activated

are the home of certain intracellular pahogens (H. capsulatum & P. marneffei)


Temporal relationship between disease susceptibility and severity, and depressed T- (thymus) derived lymphocytic function suggests that cell mediated immunity (CMI) is most important in specific host resistance to fungi. (That’s is, low T-cell fuction predisposes an individual to fungal infection.)


Fungi have enhanced pathogenicity in immunosuppresed humans (i.e. those afflicted with HIV) or in T-cell-deficient experimental animals.

Specific fungal antigens have been demonstrated to induce blastogenic transformations and release of lymphokines (CKs produced by lymphocytes) among sensitized lymphocytes. These lymphokines are presumed to function by interacting with portions of the CMI system. (Monokines are CKs produced by monocytes and macrophages.)

Lymphokine interactions function to

a) localize and activate macrophages and include macrophage migration inhibition factor and macrophage activating factor.

b) Act directly on lymphocytes as do blastogenic factor and lymphocyte chemotactic factor

c) mediate killing or inactivation of target cells via lymphotoxins


Expressions of t-cell-mediated immunity to fungi INNCLUDES:


Contact allergy (dermatitis, etc.)

Activation of macrophages and TC cells This is important because activated cells are more likely to kill fungus.

Chronic granulomatous reactions. These are the predominant tissue reaction to fungi in CMI-competent patients (that is, patients who are not immunocompromised). It is a type of DTH response the body mounts against a pathogen that it cannot kill in which large numbers of macrophages (which may fuse to become multinucleated cells which are more efficient phagocytes) congregate with lymphocytes and fibroblasts around large or numerous target fungi to wall off the pathogen and control the infection. There is generally no tissue death associated with granuloma formation.


Tests to determine the condition of a patient’s immune system are useful in prescribing treatments since patients with functional CMI don’t generally need lots of antifungal therapy.

Traditionally, skin tests assay are used to test for DTH. If the skin test is positive, then one can safely assume that the patient has a competent immune system.

There are three responses:

Ø Wheal/flare response – possibly due to IgE antibodies and exhibited within 10-30 minutes.

Ø Arthus reaction – which is mediated by precipitable antibodies which fix complement, aggregate and excite PMN infiltration and is accompanied by severe, localized immediate-type hypersensitivity

Ø DTH – a 5 mm induration (hardening) with or without erythema (reddening) at 24-48 hours

Ø If an exposed patient gives a negative response, then one can say that CMI is not functioning and it is necessary to begin therapy. If a patient goes from a negative response to a positive response, then this is a sign that the CMI is returning.

Lymphocyte Transformation assays (LT assays)

These tests involve sensitized T lymphocyte responses to specific fungal antigens as measured by (1) increased synthesis of DNA, RNA, or protein or (2) a greater number of cells of the blast type resulting form blast cell transformation. One can use peripheral blood, spleen tissue, lymph nose tissue, or other tissue which contains a sufficient number of lymphocytes.

Macrophage migration inhibition factor assays (MIF assays)

This involves sensitized lymphocytes that respond to specific antigens in vitro by production of MIF. MIF lymphokines acts to retard or inhibit migration of macrophage.

Cytotoxicity assays

This involves activated lymphocytes that release cytotoxins, which bring about lysis of target cells

All generalizations dealing with fungi must be tempered by consideration of five factors:

The fungus involved (e.g. low/high virulence)

The exact immunological state of the host

The number of infecting units involved

The route of infection

The site of the lesions involved

The duration of infection


Primary ("true") pathogenic systemic mycoses are pyogenic (pus-like) reactions followed by granulomatous reaction.

Granuloma formation is usually associated with immunocompetent hosts (those with intact immune systems). The granuloma walls off and isolated the living fungus and results in very little tissue death. The granuloma can result in a calcified lesion that may reduce (in the lungs) that may reduce the respiratory capacity of the host. If no granuloma forms, the patient may be immunocompromised.

Opportunistic systemic mycoses may result in necrosis (extensive tissue death) and suppurative (fluid-filled) lesions as well as cysts (fibrous or nonfibrous walls filled with fluid).

Generally when a pathogen invades a compromised host, the lesions that result are more severe since CMI is abrogated.


Data indicate, at least with cryptococcal system, that granuloma formation is a two stage CMI process associated with immunocompetent people:

Phagocytosis by macrophage resulting in a pyogenic (or cystic) type of reaction

Followed by another CMI step that promotes granuloma formation and possibly more killing

Proof of this two stage process lies in a study of athymic mice:

Ø WT mice infected with C. neoformans formed granuloma on liver (no cyst).

Ø Athymic mice infected with C. neoformans developed cystic lesions and necrosis.

Ø When lymph noses were transferred to athymic mice, granuloma formed.

Ø When carrageen (a macrophage blocking agent) to WT mouse cyst formed.


Primary ("true") Pathogenic Systemic Mycoses

These tend to occur in immunocompetent patients and can be characterized as follows:

pyogenic ("pus-like") reactions

followed by granulomatous reactions. Granulomatous reactions are generally associated with a functional immune system; that is, granuloma formation is often indicative of an intact (CMI) immune system. Granulomas generally form in the lungs when professional phagocytes cannot clear the pathogen form the lungs and are not associated with tissue death. These can lead to scarring or result in calcified lesions, which may reduce the respiratory capacity of the host.

Opportunistic Systemic Mycoses

Aspergillosis and Candidiasis are common in immunocompromised patients. When a pathogen invades a compromised host (with abrogated CMI), the lesions are generally more severe and can result in necrosis. These lesions can be characterized as follows:

necrotic (extensive tissue death)

suppurative (lesions may be fluid filled)

cysts – nonfibrous or fibrous walls filled with fluid. These can be contrasted to granulomas. The inability of a patient to form a granuloma may indicate the the host has an abrogated immune system and cannot mount an adequate attack on the pathogen.




The phylum Fungi Imperfecti of the subkingdom Eumycota differs from other classifications in that it is a nonphylogenetic taxon. This category contains fungi which cannot be classified because they have no known sexual states or have sexual states which have never been observed.

It was recognized that the sexual cycles of fungi, particularly of the Ascomycota and Basidiomycota, were important for understanding relationship and determining phylogeny. However, under this system there was no way to taxonomically categorize fungi that had no known sexual cycles. Creating a unique phylum of fungi in which the fungi are named based on morphological observations and naming of asexual states with little regard for relationships solved the problem.

The sexual state of a fungus is called its "perfect state" while the asexual state is called its "imperfect state", hence the term Fungi Imperfecti.

Grouping within this phylum does not necessarily reflect phylogeny – species in the same genus may be less related than species in a different genus.

Most species are, in reality, members of other phyla, particularly Ascomycota & Basidiomycota, but cannot be classified morphologically since they do not exhibit a sexual state. Most Fungi Imperfecti are probably Ascomycota based on studies of septa, etc.

Members of the Deuteromycota often have two or more acceptable scientific names.

The Fungi Imperfecti are first named according to the rules of Botanical Nomenclature for asexual (mitosporic) fungi.

When their perfect (sexual) states become known, the fungi classified as Deuteromycota are re-classified and renamed according to the rules of Botanical Nomenclature for sexual fungi. As a result, Fungi Imperfecti acquire two names and the name that is generally most prevalent is the older, inaccurate name.


If a fungus grows, it usually exhibits its asexual (anamorphic) phase first.

With medically important fungi, one can identify and treat a mycosis without knowing anything about its sexual stage or how it is classified, so there is little initiative to take the time to re-categorize.

Induction of the sexual state form the asexual state is often dependent upon inducing sex in mated self-sterile strains (heterothallic strains), which can be difficult.

Induction of sexual states often requires special environmental or physiological conditions which may not be known.


The anamorphic phase (or anamorph) is the asexual phase of the fungus. During this stage, no meiosis occurs, only mitosis.

The teleomorphic phase (or teleomorph) is the phase during which kayogamy and meiosis occur.

The holomorph is the term used to speak of both the asexual (anamorph) and sexual (teleomorph) phases.

Anamorph + Teleomorph = Holomorph

Synanomorphy (or synanomorph) is a term used to refer to the different asexual morphological phases of the same fungus. These fungi have different names because they are dimorphic in their asexual phase. For example, using molecular techniques, it has been discovered that many fungi are the same genetically. These fungi are called synanomorphs.


The Fungi Imperfecti are subdivided into nonphylogenetic form-classes.

Blastomycetes: asexual yeasts or the nonsexual yeast phases (anamorphs) of ascomycetous, basidiomycetous, or dimorphic fungi.

Hyphomycetes: asexual conidial fungi or nonsexual phases (anamorphs) of ascomycetous, basidiomycetous, or dimorphic fungi.

Coelomycetes: asexual fungi or nonsexual phases (anamorphs) of ascomycetous or basidiomycetous hyphal fungi that produce conidia in multihyphal aggregates called conidiomata (pl. conidioma). These are conidial fungi.

Mycelia Sterilia: nonconidiogenous hyphal fungi that reproduce only by fragmentation. These grow vegetatively only, they never make spores.


If each thallus of a fungus is self-sterile and requires mating with a compatible strain to reproduce sexually, that fungus is called heterothallic. Heterothallic is a term used to describe fungi which have haploid strains which are self-sterile, that is, they must mate with a strain of the opposite type and then undergo meiosis to produce meiotic nuclei, which get packaged into ascospores or basidiospores. Homothallic fungi are fungi in which each thallus can reproduce without mating with another thallus. Most medically important fungi are heterothallic.


Recently, molecular techniques have been used to determine the phylogeny of the Fungi Imperfecti, which means that the phylum may become obsolete. This means that hundreds of fungi are renamed as more and more of their sexual states are discovered.

Though this is not a bad thing in itself, it results in a greater resistance to learning and understanding the naming and significance of the re-classification. Generally, both the imperfect and perfect names of the fungi are used, which creates confusion. This is particularly true in applied fields such as medical mycology, plant pathology, and industrial mycology.



Fungi are eukaryotic, heterotrophic, osmiotrophic organisms which have cell walls, typically reproduce asexually and/or sexually by forming spores, and grow either reproductively by budding (as in yeasts) or nonreproductively by hyphal tip elongation (as in molds)

*note: this definition is not100% accurate, it doesn’t exclude some fungal-like protists which produce zoospores


Identification, based on recognition

Classification, determines relationships between specimens and reflect phylogeny/evolutionary history

Nomenclature, the naming of specimens


Organisms in the same taxa are more related than are organisms in different taxa.

Kingdom à Fungi

Subkingdom à ______mycotera

Phylum à ______mycota

Subphylum à ______mycotina

Class à ______mycetes

Order à ______ales

Family à ______aceae

Genus à ______

Species à ______

*note: Genus and species names are in italics because the are in Latin.


Different types of fungal-like protists and fungi are classified based on the sort of spores they make. There are several different types of spores.

A spore is a microscopic propagating unit without an embryo. One way to classify spores is based on the way they are derived, either through mitosis or meiosis. Mitospores are spores which result from mitosis. Meiospores are spores which result from meiosis.

Zoospores are non-walled, flagellated cells derived by mitosis (mitospores). Note that they have flagella, which means that they are motile. (Recall, also that eukaryotic flagella have a "9+2 microtubule" structure.) They must encyst and acquire dormancy qualities before they become true spores.

Sporangiospores are nonmotile spores which (like zoospores) are derived by mitosis (mitospores).

A sporangium (or mitosporangium)is a cell in which mitotically derived reproductive cells are produced by cytoplasmic, vesicle-mediated cleavage to produce mitospores (zoospores or sporangiospores). A meiosporangium produces meiospores.

Zygospores are diploid spores which undergo meiosis upon germination.

Teliospores are spores which contain two nuclei of the opposite mating type (dikaryotic spores). Germination of the spores results in karyogamy followed by meiosis.


As few as 20 years ago, the classification "Fungi" represented a heterogeneous grouping of absorptive, heterotrophic eukaryotes which were distantly related and probably had no common ancestor. All sporangial organisms were placed in the same class. All sporangial fungi and sporangial fungal-like protists were once erroneously classified under into the fungal class Phycomycetes. Today, we realize that these organisms represent members of four to ten phyla in three kingdoms.

Fungi and fungal-like protists can be thought of as mitosporangial (meaning that they produce spores using mitosis alone) or nonmitosporangial (meaning that they produce spores via meiosis). Mitosporangial organisms are considered to be "lower fungi" and produce zoospores and/or sporangiospores. Nonmitosporangial fungi are considered "higher fungi".


The kingdom Protoctista contains some organisms that resemble fungi.

These fungal-like protists are classified in the phylum Plasmodiophoromycota. Plasmodiophoromycota produce zoospores which each have one whip-lash flagellum and one stub.


The kingdom Chromista also contains some organisms that resemble fungi.

These fungal-like protists are classified in the phyla Hyphochytridiomycota and Oomycota. The Hyphochytridiomycota produce zoospores which each have one anterior tinsel flagellum while the Oomycota produce zoospores which each have one whip-lash and one tinsel flagellum.


The kingdom Fungi contains three subkingdoms:

The subkingdom Mastigomycotera contains fungi which are zoosporic (that is, produce flagellated spores). This subkingdom contains the phylum Chytridiomycota, which are fungi that produce zoospores (each with a posterior whip-lash flagellum).

The subkingdom Amastigomycotera contain fungi which are non-zoosporic (that is, produce spores that lack flagella). This subkingdom contains the phylum Zygomycota, which are fungi that produce nonmotile sporangiospores and/or zygospores.

The subkingdom Eumycotera contains non-sporangial fungi. They are found as yeast or filamentous fungi and are classified based the presence or absence of structures called asci and basidia.


Plasmodiophoromycota - produce zoospores which each have one whip-lash flagellum and one stub

Hyphochytridiomycota - produce zoospores which each have one anterior tinsel flagellum

Oomycota produce zoospores which each have one whip-lash and one tinsel flagellum

Chytridiomycota - produce zoospores (each with a posterior whip-lash flagellum)






The fungi classified as Chytridiomycota probably define the boundaries between the fungi and the protists. Mycologists believe that they are the main line of evolution to higher fungi based on studies of lysine synthesis. There are two pathways organisms can utilize to synthesize the amino acid lysine: DAPA and AAA. Plants, bacteria, nad other organisms use the DAPA pathway, while the Chytridiomycota and other fungi use the AAA pathway.

Also, RNA-sequencing has been used to show that zygomycetes, ascomycetes, basidiomycetes, and chytridiomycetes are along the same line of evolution.


The subkingdom Eumycotera contains most of the pathogenic fungi. The fungi are further classified into phyla based on the presence or absence of asci and/or basidia.

The phylum Ascomycota contains fungi which produce endogenous meiospores, known as ascospores, in a cell(s) called an ascus (asci). The ascus is called the meiosporangium of Ascomycota because it parallels the role that a sporangium plays in the production of mitospores, but produces meiospores instead. These fungi are regularly septate hyphal (that is, their hyphae are walled off at regular intervals) or yeast fungi.

The phylum Basidomycota contains fungi which produce exogenous meiospores called basidiospores on a structure called a basidium. The basidium is called the meiosporangium of Basidiomycota. These fungi are also regularly septate hyphal or yeast fungi.

The phylum Fungi Imperfecti (Deuteromycota) contains fungi that are regularly septate hyphal fungi or yeast fungi which are not known to produce meiospores (no ascospores or basidiospores)

It should be noted that sexual reproduction in fungi involves three phases

plasmogamy – the fusion of protoplasts

karyogamy – the fusion of two nuclei



The ascocarp is a multihyphal aggregate in which (or on which) asci form. The Ascomycota can be further classified into three subphyla based on lack of ascocarp or the type of ascocarp exhibited.

The subphylum Hemiascomycotina contains Ascomycota that lack ascocarps (nonascococarpic ascomycetes I).

The subphylum Archiascomycetes also contains Ascomycota which lack ascocarps (nonascocarpic ascomycetes II).

The subphylum Euascomycotina contains Ascomycota that have ascocarps (ascocarpic ascomycetes). Within this subphylum, fungi are further classified into four classes according to the type of ascocarp that develops.

Class Plectomycetes: produce a cleistothecium, a spherical structure with no pores that releases spores by rupturing.

Class Pyrenomycetes: produce a perithecium, a structure with a cavity in which meiosis occurs to make eight spores.

Class Discomycetes: produce an apothecium, a cup-shaped structure. The asci form on the surface of the base.

Class Loculascomycetes: produce loculoascostroma, which are masses of aggregated hyphae in which cavities form. These cavities hold asci.















The basidiomycota can be classified into subphyla based on teliospore production. Heterobasidiomycotina produce teliospores while Holobasidiomycotina do not. The Heterobasidiomycotina subphylum contains fungi classified as rusts (Urediniomycetes) and smuts (Ustomycetes). The Holohbasidiomycetes subphylum contains Phragmobasidiomycetes (jelly fungi & septate basidial fungi) and Holobasidiomycetes (mushrooms).



Dermatophytes / ringworms cause infections in humans known as tineas, infections produced by dermatophytic fungi growing in the keratinized tissue of man and other animals.

The dermatophytes (dermatophytic fungi) are a large, closely related group of keratinophilic fungi which cause infections of hair, skin and nail. They are Fungi Imperfecti of the form-class Hyphomycetes, the form-family Moniliaceae, and the form-species Microsporum, Trichophyton, and Epidermophyton. Dermatophytes tend to stay localized to the skin because they can live on the skin, where it is cooler, but cannot grow at the elevated temperatures found inside the body


Dermatomycoses refer to any mycosis of skin and hair.

Dermatophytoses are a subset of dermatomycoses which:

Include several clinical entities (known as tineas) which indicate the anatomical site of infection. Tinea is a clinical term, not a taxonomical name. Therefore, a tinea can be caused by different species of fungi.

Have a pathology with is initially eczemaform (itchy) and followed by DTH allergic inflammatory responses. (The DTH response is usually a reaction against metabolites the fungus has secreted.)


Ø The Greeks called the lesions herpes, for "circular lesions".

Ø The Romans called the lesions tineas ("small insect larvae") because they thought they were caused by larvae burrowing into the skin.

Ø In the early 1800’s, there was a favus epidemic in Europe. Favus caused inflammation and scarring of the scalp and caused hair follicles to crust and ooze. It was such problem that many scientists Remark, Schoenlein, Gruby, etc.) of the age were dedicated to finding the cause of the disease and a cure.

Ø Though he didn’t publish his idea immediately, Remark (1830) was the first person to believe that the sorts of lesions described above were caused by a fungus. He observed arthroconidia and hyphae in the hair shafts of patients afflicted with favus (a skin ringworm condition).

Ø Schoenlin (1839) used Remark’s notes to formally publish evidence that favus was caused by a fungus.

Ø In 1840, Remark published his observations confirming Schoenlein’s conclusions and also carried pout a successful self-inoculation (which indicated that a fungus did indeed cause favus). He named this fungus T. schoenleinii.

Ø From 1830-1840 Gruby also published a series of papers that independently confirmed and extended Remark’s and Schoenlein’s conclusions. Specifically, these papers made five important points:

They confirmed a fungus causes favus.

They described beard dermatophytosis (caused by a fungus later named M. mentgrophytes by Robin in 1853.)

They described an epidemic of prepubertal scalp ringworm caused by M. audouinii

They recognized that there were three distinct types of scalp ringworm.

They also described the isolation of the favus fungus on potato slices, it culture, and its subsequent ability to cause infection (via self-inoculation).


The Fungi Imperfecti classified as Microsporum and Trichophyton would be classified as the true genus Artrhroderma if one could induce sex in these organisms.

The genus Arthroderma contains heterothallic and dimictic fungi. (the tem dimictic means that these organisms need opposite mating types in order to sexually reproduce and mating is controlled by a single set of compatible genes at a single mating-type locus.)

Branching of the Arthroderma



Holomorphs / Teleomorphs

Those with know sexual states

Fungi Imperfecti / Anamorphs

Those that have not been induce to sex

Phylum: Ascomycota Form-class: Hyphomycetes
Subphylum: Euascomycotina Form-order: Moniliales
Class: Plectomycetes Form-family: Moniliacea
Order: Onygenales Form-genera: Epidermophyton, Trichophyton, Microsporum
Family: Gymnoascacea / Arthrodermatacea  
Genus: Arthroderma  

The class Plectomycetes can be further divided into the orders Onygenales and Eurotiales.

Onygenales have a gymnothecium, prosenchymatuos plectenchyma (a ascocarp wall made of loose hyphae) and produce thalloconidia. This order also produces prototunicate asci, which are spherical, contain 8 ascospores, and are scattered randomly.

The Eurotiales have a clestithecium, pseudo parenchymatous plectenchyma (an ascocarp wall with compacted hyphae that closely resembles a tissue-like structure) and produce phialoconidia.


Too much work because:

All sexual strains are heterothallic and dimictic.

Tester strains would have to be maintained.

The most common pathogens of man are , so far, only known as imperfects.

Treatment is usually possible without knowledge of the absolute identity of the species.

Species identity most important for epidemiology-type studies. DNA identities will help.


Ø Geophilic species are those associated with the soil.

Ø Zoophilic species are those associated with furry animals.

Ø Anthropophilic species are those associated with man. These often exhibit a certain sporulation pattern only in human hosts.

Ø Theoretical evolution of anthropophilic fungi:

· Group of soil saprophytes became adapted to keratin utilization (possibly on skin scales or shed animal hair). This may have conveyed an advantage because it provided these fungi with a source of nutrition not widely utilized in nature.

· Some of these fungi became associated more directly with furred animals and gained the ability to form transient infections.

· A subset of these fungi adapted to growth on the keratinized zones of animals and man.

· Some of these fungi equilibrated with the host so that only slight host reactions occurred.

· Of these, a few developed specialized methods of reproduction different that their geophillic cousins which included the formation of specialized types of arthroconidia in hair and possible the loss of frequent sexuality.

· Finally, some of these became associated more or less specifically with certain hosts, including man. This may be due to the utilization of different keratins by different species, segregations of strains and species over time, and/or the loss of a mating type.

Ø Dermatophytic species generally stay localized to the skin and only rarely invade deeper tissues since they cannot tolerate higher temperatures.


Ø Ectothrix invasion involves a dermatophytic fungus which has hyphae that fragment into arthroconidia on the surface of the hair shaft. They may also fragment just beneath the hair cuticle which may require a "hair-penetrating organ" (a mechanism hyphae use to penetrate hair.

Ø Endothrix invasion involves a dermatophytic fungus which has hyphae that fragment into conidia within the hair itself.

Ø Favus is a condition in which there is no conidiation in or on hair.


Discomfort during this type of fungal infection is usually due to a DTH response against fungal metabolites in hair follicles. Though dermatophytes may be found on other parts of the body (groin, etc.), it is rare. There are four kinds of tinea capitis which involve the hair and affect the scalp:

Prepubertal, "gray-patch", "classical scalp ringworm", "epidemic ringworms".

These are exothrix invasions of the hair involving small, holoarthric conidia are generally caused by M. audouinii and M. canus.

· Associated with small boys

· Gray-patch refers to hair areas becoming grayish, lusterless and discolored within the first days of infection. These gray hairs eventually weaken and break off in masses leaving gray patches.

· Itching may be mild to severe. M. canus, a geophilic species, usually results in more inflammation than M. audouinii, which is the most common cause of gray-patch.

· Spontaneous cures frequently corresponded to the onset of puberty indicating a possible link between hormones and infection.

· An infected person is Wood’s lamp +, meaning that hair fluoresces brilliant green due to pteridenes in hyphae.

· Cures: epipilation, X-ray/epipilation, topicals, griseofulvin, azoles.

Black dot. This is an endothrix invasion of the hair involving large holoarthric conidia and is caused by Trichophyton species.

· Relatively few hairs are involved, but infected hairs break off sharply leaving a stub, which creates the illusion of a black dot on the scalp. Spores often ooze from this stub.

· Infected persons are often Wood’s lamp –

· In the U.S. the main causative agent is T. tonsurans. Case numbera are increasing de to extensive inmigration form Central and South American countries.

· Treatment: Griseofulvin (with or without topical azole), allyyaminaes/terbinafine, or topical/oral azoles.

Favus. This does not involve conidiation of hair and is caused by T. scholenleinii.

Nondescript. This is a rare type of tinea capitis caused by Trichophyton infections and is generally an ectothrix type of invasion.


Tinea corporis is a ringwom of the glabrous skin other than the groin and periannal regions which is almost always restricted to the stratum corneum. In the U.S. it is motly caused by T. rubum, T. mentagrophytes, and M. canis.

Clinical symptoms are almost totally due to fungal metabolites (such as pteridenes) acting as allergens or toxins and eliciting a DTH response. Fungi grow outwards in a circular fashion (centrifugal spread). The regions of infection with the most nutrients available to the fungi (the periphery) are the regions in which the most fungal metabolities are concentrated. This is where the greatest DTH response can be observed in the shape of a ring. There is a clearing of metabolities inside the "ring" followed by re-infection (hence, the term ringworm).

Lesions can be either scaling or pussy, though they are generally not terribly itchy. Deep granulomas are very rare. Very high inflammatory response may produce vesicular lesions which sometimes (rarely) yield a spontaneous cure.

Infection rates are high in localities with a high incidence of tinea capitis.


Tinea imbricata is another type of tinea corporis caused by T. concentricum. It is characterized by polycyclic lobed ring patterns accentuated by the raising of skin scales at the margins.

It is associated with the pacific islands and, based on certain studies, it is speculated that it was introduced to the New World by pre-Columbian explorers. Among certain cultures, the fungus is often purposely passed form mother to daughter to establish beauty marks, which leas to chronic, life-long disease. Antifungal cures are often followed by severe remission.


This disease is similar to tinea corporis and tinea imbricata, but is restricted to the groin and periannal regions. In the U.S. the most common causative agent is T. rubrum. It is associated with conditions of high humidity and abrasive clothing.

Infection can be acute or chronic and is often pruitic (itchy). Lesions are usually delimited with a single, raised, erythematous margin (a single ring) and tend to be dry & scaly.


Tinea pedis is a fungal infection of the foot which is generally caused by T. rubrum and T. mentagrophytes.

It can be interdigital (between the toes), vesicular (pustular), or hyperkeratotic-erythrodermic (involving darkening of the skin which may be permanent).

Treatment usually involves topical/oral azoles or other antimycotics.


Tineas manuum is a ringworm of the hands. This often arises when a person afflicted with athlete’s foot scratches his feet and infects his own hands. It is generally associated with the same severe, prurtic symptoms of tinea pedis and treatment is the same.


Tinea unguium is ringworm of the toenails and fingernails which often occurs after injury to the nail. In cases of infection, the fungus invades the quick of the nail. It is commonly associated with tinea pedis on the feet. Treatment often includes oral itraconazole or terbinafine.



Aspergillosis is an opportunistic disease involving a member of the form-genus Aspergillosis. Aspergillosis is generally initiated when conidia are inhaled and germinate into hyphae, which invade lung & systemic vessels. If host defenses fail, hyphae break off & disseminate to other organs. The main predisposing factor of Aspergillosis is neutropenia, a reduction in the number of PMNs

Aspergillus is a large form-genus with phialidic anamorphs (conidia produced by enteroblastic phialides). Teleomorphs are known as (psuedoparenchymatous) Plectomycetes, Eurotiales, and Eurotiaceae.

Main agents of Aspergillosis are:

1) Aspergillus funigatus (which is responsible for 80% of cases. The fungus is uniserate and its thermophilic qualities may be considered virulence factors.)

2) A. flavus(biserate)

3) A. niger (biserate)

4) A. terreus (biserate)

5) A. ochraceus

6) A. niulans (This is a homothallic plectomycete of the Urotiales order)

7) A. clavatus


Toxicity due to ingestion of moldy food

Allergy and sequelae to conidia or transient hyphal growth in body orifices

Colonization without invasion into preformed cavities or debilitated tissue

Disease of lungs and other tissue

Systemic and fatal dissemination disease

Alfotoxin, a potent carcinogen found in grain, is associated with Aspergilloisis


Traditionally identification is based on morphological characteristics of anamorphs such as

colony morphology / color

conidiophore & phialide morphology (whether the fungus is uniserte or biserate)

conidium morphology (A. fumigatus is thermotolerant up to 45*, while other speciescan wthsatand temperatures only within the 37-40* range.)

Aspergillosis can be identified based on characteristic dichotomous branching hyphae.



Allergic. This is usually a response to conidia which are controlled by macrophages and don’t germinate The response is IgE-mediated and treatment usually revolves around anti-allergy treatments.

Colonizing (Aspegilloma). This form is usually found in individuals with repeated exposure to the fungus. (i.e. Farmer’s Lung) Treatment usually involves intensive anti-fungal therapy

Invasive. This form is usually due to lowered resistance of the host caused by disease or drugs. Amphotericin B is generally used.


Ø Disseminated


Ø Cutaneous

Ø Nasal

Ø Iatrogenic

Ø Otomycosis – colonization of ear drum, which may also have bacterial overgrowth



Superficial Mycoses

These are mycoses which generally do not elicit a host cellular respose, cause no tissue damage, or make the host aware of the fungus. Since the fungi which cause these diseases are benign and often considered normal flora, superficial mycoses cannot be considered true examples of disease (though they can cause disease in immunocompromised hosts).

Cutaneuous Mycoses

Dermatophytoses or ringworm is caused by Plectomycetes, which can cause eczema followed by allergic and inflammatory skin reactions. These agents are included in the form-genera Microspoium, Trichophton, and Epidermophyton.

Cutaneous candiasis is caused by skin and mucotaneous tissue infection by Candida species

Dermatomycosis is caused by non-dermatophytes other that Candida species

Subcutaneous Mycoses

These mycoses are a large group of diseases found in normal (immunocompetent) hosts which tend to be chronic and initiated by traumatic implantation offungi with relatively low virulence. These can cause granulomatous reaction in normal hosts, but they can also cause severe illness in compromised hosts.


The development of antifungal agents was slow relative to the development of antibacterial drugs for several reasons:

Systemic fungal infections(until recently, due to large number of IC patients) have been considered rare

Drug companies often determine that the cost of development and testing did not seem to warrant extensive efforts of find cures/treatments for mycoses. Over the last ten years (due largely to the AIDS epidemic), however, there has been new interest due to the increased number of immunocompromised patients.

Establishment of dependable animal models for testing antifungals has been difficult.

Both human hosts and fungi are eukaryotes, which makes treatment difficult.


Traditional difficulties related to identifying fungal infections delayed treatment until patient became too ill to be helped.

MD’s selection of drugs was very limited and of those agents that were available, few had known modes of action. (The mechanisms by which these drugs worked were difficult to determine since only a few drugs were available to test and there were only a small number of clinical cases.)

MD’s generally were reluctant to use antimycotics with serious known or claimed liabilities.

Ø Note: Amphotericin B is the best drug available today, though it has lots of side-effects.


Polyene macrolide antibiotics

The major members of this class are Nystatin and Amphotericin B (amphiliposomes). Ampho B is nerphrotoxic.

Ergosterol Biosynthesis-Inhibiting Antifungals

These include synthetic imidiazoles, triazoles, and related compounds. These treat various fungal infections by inhibiting demethylation of lanosterol so no ergosterol can be made. Azoles bind cytochrome p450 w different affinities through the N4 position of the triazole ring as a sixth ligand for the heme iron. The major members of this family are:

Miconazole – found in micitin and used to treat Candida

Ketoconazole – a imidiazole that was the first therapeutically useful drug

Fluconazole – a triazole found in diflucan and can be used for maint. therapy

Itraconazole – a triazole found to be less toxic and more effective than both Ketoconazoel and Fluconazole. Unlike K. & F> it can be used against Aspergillosis. It can contribute to heart failure.

Terbinafine – in Lamisil



Ketoconazole, Fluconazole, & Itraconazole are oral drugs which are replacing Ampho B therapy in some cases.

Griseofulvin – used in human and veterinary medicine

5-Fluorocytosine – used often in combination with other antifungal drugs, especially Amphotericin B

KI – used for sporotrichosis

Glucan Sythase Inhibitors

These include Capso fungin and FK463

In 1949 Brown and Hazen discovered 2 antifingal activities associated with culture broths of Streptomyces noursei: Actidione & Nystatin.

Actidione ("act of God") was first thought to have many attributes that made it ideal for anti fungal therapy including high solubility and a broad spectrum of antifungal therapy. However, it was found to be highly toxic to animal cells and therefore had no therapeutic use.

It is an inhibitor of eukaryotic protein synthesis (is a peptidyl transferase inhibitor).

Nystatin, which was named for the NY State labs in which it was discovered, was found to be almost completely insoluble, and didn’t seem to have a widespread range of antifungal activity.

It is an anti-Candida agent (with polyene structure) used mainly for treatment cutaneous and mucotaneous candidiasis. It is commonly used to treat intestinal and vaginal overgrowth to control candida.

It is making a come-back because it is being reformulated into a lipid complex. Since it is insoluble, it cannot be absorbed and is oftn found intopical medication.

Strudture of Nystatin: It is a degenerate heptaene (has only 6 double bonds, one missing). It has hphobc & hphilic sides The sugar moiety is mycosamine.


Like Nystatin, Ampho B has the mycosamine sugar moiety and hphobic hphilic sies. It is the gold standard for life-threatening systemic mycoses.

It was marketed as Fungizone and Mysteclin F. Mysteclin F was added to tetracycline ( which can cause Candida overgrowth) as anti-acne / anti candidal preparation . This was replaced by Acutane.

Supplidd as microcrystals – very fine srystals used therapeutically because increases solubility.

When used, one must monitor the GRF and BUN for signs of nephotoxicity

It is generally administered IV.






Though there is no strict definition, pathogenic yeasts are most accurately defined as fungi that:

grow predominantly as yeasts (through the vegetative process of budding)

may be monomorphic (which is rare), dimorphic, or pleomorphic/polymorphic.

Do not produce conidiophores or conidia (that is, they are not yeast phases of Hyphomycetes). Note: This does not apply to the dematiaceous species.

Tend to be asexual, though when sex is exhibited the majority are found to be members of the Hemiascomycotina

One major "pathogenic yeast" is a known Heterobasidiomycota member and contains dolipore septa and clamp connections. (Malessezia and Trichosporon species represent suspected Heterbasidiomycetes.)


The term "pathogenic yeasts" is not a taxonomical term. The fungi in this category contain both sexual fungi (teleomorphs/holomorphs) and nonsexual fungi (anamorphs).

Sexual fungi (teleomorphs/holomorphs):



Yeast forms of Euascomycotina (mostly dimorphic, hyphal, conidiogenous species)

Yeast forms of some Zygomycota

Nonsexual Fungi (anamorphs)

Fungi Imperfecti


Yeast forms of dimorphic Hyphomycetes



Candida (suspcetd ascomycetes)

Cryptococcus (known basidiomycete)

Malesezia (suspected Basidiomycete)

Trichosporon (suspected Basidiomycete)

Ascomycota – all of the ??? listed below are members of Hemiascomycotina)






Filobasidiella (suspected Phragmobasidiomycete)




Sporotrichosis is a chronic mycosis caused by Sporothrix schenckii. The fungus is thermally dimorphic, meaning that temperature determines whether it grows as yeast or mold. At 37*, the fungus can be found as a budding yeast within the host. (Conidia are holoblastic.) In the mold form, hyphae aggregate and grow unidirectionally in a fashion reminiscent of rhizomorphs. S. schenckii is also a dematiaceous fungus, but is not a member of the black yeast "clade". It exhibits regulated melanin biosynthesis via the DHN pathway. Melanin is thought make spores more pathogenic.

Taxonomy: Sporothrix schenckii (anamorph) is a member of the hyphomycetous form-class of the Fungi Imperfecti. Based on septal structures (revealing a single septal pore and Woronin bodies), it is a suspected Ascomycete with a "hybrid" ascocarp – it appears to have characteristics of both pyrenomycetes and plectomycetes (a prototunicate ascus containing eight scattered ascospores). 18s rDNA analysis revealed it to be a pyrenomycete. It can be classified among the Ascomycota as follows:

Phylum Ascomycota
Subphylum Euascomycotina
Class Pyrenomycetes
Order Ophiostomatales
Family Ophiotomataceae

Pathology: S. schenckii is a primary pathogen and infection is characterized initially by nodular lesions of the cutaneous and subcutaneous tissue and adjacent lymphatics which suppurate, ulcerate and drain. These nodular lesions are closed cyst-like sacs under then skin. Eventually, the nodule progresses and attaches to overlying tissues resulting in suppuration, ulceration, etc. It is thought that the fungus may enter the lymphatics by first being phagocytosed by a macrophage. Systemic forms of the disease are rare, but have been documented. Infection is usually due to traumatic implantation into the tissue though primary lung infection may occur.

Treatment: Treatment usually involves super-saturated KI or, in more extreme cases, oral EBIs (such as ketoconazole and itraconazole) and Amphotericin B.

There are several major differences that distinguish sporotrichosis from chromoblastomycosis, pheohyphomycosis, and mycetoma:

The main agent of disease is S. schenckii, though S. cyanescens has been suspected in some cases. These are both hyphomycetous molds. (Chromoblastomycosis, etc. involve filamentous fungi.)

Sporotrichosis is generally associated with lymphatic involvement and initial nodular lesions.


Most cases of sporotrichosis are the lymphocutaneous (gummatous) type, though fixed cutaneous infections are common as well. In the tissue, asteroid bodies may form, in which case eosinophilic substances radiate from the yeast cells.

Lymphocutaneous. In this form, the first sign of infection after trauma is nodule formation as described above. This form has the following pathology:

Ø Traumatic implantation of fungus

Ø Formation of small, hard, moveable, non-tender and nonattached subcutaneous nodule

Ø Attachment of nodule to overlying skin, which eventually becomes discolored (pink à purple à black)

Ø Lesion ulceration gives rise to a "sportrichotic chancre"

Ø Usually, there is continued ulceration and chronic spread via the lymphatic channels, though spontaneous cures have been documented.

Fixed Cutaneous. These infections stay localized for years without lymphatic involvement. There has been speculation that hosts my be immune protected

Mucotaneous. In these rare cases, mucosal tissues get infected.

Extraneous and Disseminated (very rare)

Primary Pulmonary. These infections are often hospital acquired and may be associated with smoking. Serology of sporotrichin (a yeast cell antigen) is strongly positive for pulmonary form of the disease. There are 2 types of pulmonary sporotrichosis:

Chronic cavitary type is characterized by the formation of thin-walled cavities in the lung tissue after and acute case of pneumonitis

Lymph node type is acute and rapidly progressive, but resolution of lesions and recovery are frequent.



Mycetoma is a localized, progressive, tumerous, draining lesion of the skin, subcutaneous tissue, muscle, fascia, and bone caused by aerobic actinomycetes and fungi which form compact mycelial aggragates called "grains" within infected tissue after traumatic implantation.

Grains are compact hyphae that cause tumor-like appearance. They plug up draining lesions and may cause elephantiasis.

Dematiaceous myectomas are caused by Exophiala jenselmei and Madurella mycetomatis.


Subcutaneous inoculated area slowly enlarges as a result of inflammation and fibrosis

Abscesses develop and multiple sinus tracts eventually erupt to skin surface

The sinus tracts discharge fluid (and, on occasion, even a grain)

Organism invades deeper, including bone

Draining tracts remain open

Swelling results and yields enlarged appendage



Histoplasmosis is defined as a granulomatous infection initiated as a primary pulmonary disease that may range in severity from subclinical to acute, chronic or systemic and is caused by the intracellular pathogen Histoplama capsulatum, the anamorph of Ajellomyces capsulatum (a cleistothecial ascomycete)

Histoplasmosis is a primary, endemic mycosis. It is also considered a primary pulmonary mycosis since it is generally initiated through inhalation of spores and is highly virulent. Inhalation of a small number of spores results in benign infections. Inhalation of a large number of spores may result in acute pulmonary histoplasmosis.

Histoplasmosis is the only disease caused by a fungal intracellular pathogen other than Penicillium marniffei.

Histoplasma produces both microconidia (which tend to be white) and macrocondia (which tend to be brown). The microcondia are considered to be most infectious since they are smaller and more likely to be inhaled. Holoblastic macroconidia have tuberculi on surface. Microconidia also have tuberculi, but these are less prominent. Yeast cell budding results in narrow neck (compare to blastomyces, which has a long neck).

The fungus was named histoplama capsulatum because it appears to have a capsule (though it does not) and it is associated with intracellular growth in histiocytes. The capsule appearance is due to the organism "shrinking away" from host tissues leaving a region that resembles a capsule.

Resolution generally results in protective immunity.

Synonyms: Darling’s disease, Cave fever (Spelunker’s disease), Ohio Valley disease (which is endemic in certain regions of the Ohio/Mississippi Valley)

African forms of the disease include Histoplasmosis dubosii and Large cell Histoplasmosis. In Africa, the endemic region is near the equator.



Histoplasmosis is caused by n ascomycetes rather than a basidiomycete.

Resolution of the primary pulmonary form of histoplasmosis results in protective immunity (not observed in Cryptococcosis).

The anamorph of Histoplasmosis is a dimorphic hyphomycete. (Tissue dimorphism is displayed. That is, the organism takes on a different form in vivo than in vitro.)

Histoplasmosis is associated with certain endemic regions while Cryptococcosis is not.

Histoplasma is considered to be an intracellular pathogen of the RES.


Opportunistic forms were considered fatal

Both are often associated with birds. Histoplasma – European starling. European starling proliferated in Ohio River Valley and carried Histoplasma. Crypto – pigeon

Both are AIDS-related mycoses


Benign Forms

Low dose – mildly symptomatic or asymptomatic.

Heavy dose – acute resolving or acute, disseminating resolving (results in protective immunity).

Opportunistic Forms

Chonic progressive lung disease

Chronic cutaneous systemic disease

Acute, rapidly fulminating disease

AIDS disseminated or extrapulmonary

Diagnosis is usually based on skin tests, immunodiffusion test, CF tests, etc. Calcified lesion can be observed using x-rays and autopsy.


Ajellomyces capsulatus

Phylum - Ascomycota

Subphylum - Euascomycotina

Class - Plectomycetes (forms cleistothecia)

Order - Onygenales (blastoconidium)

Family - Gymnoascaceae

Ajellomyces capsulatus var. capsulatus

Ajellomyces capsulatus var. duboisii

The fungus is heterothallic (self-sterile) & dimictic (mating controlled by single pair of indiomorphic sequences at same locus)

Onygenales is currently same order as Arthroderma

H. capsulatum var farciminosum of horses most likely also a variety of A. capsulatus

The fungus is thermally dimorphic and is found in yeast form in host. The conversion of hyphae to yeast involves the formation of oidial yeast cells.



Fulminant of children – rapid pregression, usually fatal. Macrophages increase and clog capillaries resulting in circulatory collapse.

Chronic disease of adults – usually involves a few organs and requires antimycotic therapy or surgery.

Fulminant of Adults – associated with immunosuppression


Usual (low) dose – asymptomatic, skin test conversion, X-ray findings

Symptomatic – mild symptoms, but more severe cases shoew one or more lesions in lungs. Lesions become calcified when resolved.


General: symptoms, serology, ID by morphology or gene-probe (accu-probe)


Complement fixation test (1:8 is presumptive for Histoplasmosis, > 1:32 is strong evidence of disease)

Immunodiffusion test – detects precipitins against protein antigens of histoplasmin. H band indicates active infection. M band indicates past infection.

Latex Agglutination test – detects circulating Ab using histoplasmin-coated latex particles.

FA stains


Bengin Forms– bed rest

Opportuinistic Forms– Ampho B and/ or surgical excision of cavities or masses.





Cryptococcosis is defined as a chronic, subacute or rarely acute pulmonary, systemic, or meningitic infection caused by Cryptococcus neoformans, the blastomycetes encapsulated anamorph of Filobasidiella neoformans (a basidiomycete). The fungus usually grows as encapsulated budding yeast. Cryptococcosis remains the most common fatal infection involving the CNS in patients with AIDS and is considered an opportunistic disease. Infection is usually due to inhalation of infectious agent and is therefore generally initiated in the lungs.

There are some cryptococcus strains without capsules, but these strains are not as virulent as the wild type, which has a capsule.

Synonymns of Crytococcosis include: Busse-Buschke’s disease, European blastomycosis, Pigeon breeder’s disease.


There are 4 serotypes based on the antigenic nature of capsular polysaccharides. The variety status recently changed so now there are three varieties. Serotypes A & D are associated with pigeons and AIDS because these strains are more virulent.

A called var. grubii

B (found in southern California) and C (mostly tropical) are called var gutti.

D is called var. neoformans.

Kwon-Chung found differnences in basidiospores morphology among A, B, C, & D.

A &D – var neoformans

B & C – var bacillispora

Glucose-xylose-mannose polysaccharide construction – fungus contains glucose, xylose and mannose in some combination.


This clarified many aspects of the "unusual biology of this form species.

This clarified why serotype might be geographically correlated and environmentally localized.

This clarified why pigeon handlers seemed to have propensity for pulmonary disease prior to onset of Cryptococcosis (because of A serotype associated with pigeons)

This suggested that smaller size of basidiospores (as compared to yeasts) might also often initiate infection, though dried, dehydrated yeasts (which are smaller than growing, hydrated yeasts) usually thought to initiate infection in lungs by being phagocytosed.


The teleomorph Filobasidiella neoformans (which includes the varieties var. neoformans and var. bacillispora) is a basidiomycete of the class phragmobasidiomycetes (though this is controversial) and may be belong to either the Tremellales or Filobasidiales order.

The anamorph C. neoformans (which includes the varieties var. neoformans and var. gatti) produces brown colonies due to caffeic acid and phenol oxidase.

Var neoformans (serotypes A & D) is considered the most virulent. Serotype A is found in the US.

Var gatti (serotypes B & C) are considered less virulent and are found in Southern California.

The primary infecting units may be basidiospores (because they are so small) though basidia, basidiospores and dried yeast cells are infectious.

Strains are heterothallic (self-sterile)

Since the fungus is a basidiomycete, it contains haploid strains which undergo clamp and basidium formation under N-starvation. The clamps maintain the dikaryotic condition. Germ tubes come together and conjugation occurs and mating results in a dikaryon. Once the dikaryon is formed, hyphae form clamps to maintain the dikaryotic condition.


There are two main forms of disease: a primary pulmonary form and an opportunistic form.

Primary Pulmonary Forms

Primary forms in normal hosts are rapidly resolved with minimal symptoms. This is probably initiated by inhaling basidiospores or dried yeasts in low numbers. There is no evidence that exposure results in long-term, protective immunity. Inhalation of larger numbers of yeast or spores may yield acute, chronic symptomatic infections with infrequent spread to other body sites (i.e. CNS)

Chronic forms of pulmonary infection in normal hosts (which are generally due to long-term, repeated exposure to relatively low doses of the infectious agent – i.e. Pigeon Breeder’s disease) may result in cutaneous or meningitic involvement

Primary pulmonary forms are generally asymptomatic, but symptoms may include cough, fever, etc. Resolution rarely result sin scars. Definitive identification of disease depends on isolation of organism and/or latex agglutination test (which is very good for Cryptococcosis) for cryptococcal antigens or fluorescent antibody of biopsy.

Treatment of pulmonary Cryptococcosis:

1) Amphotericin B alone or in conjunction with 5FC. Try fluconazole or other azoles (if these drugs don’t work. Combination therapy may be effective. Diflucan is often used as effective maintenance therapy.

2) Surgical removal of lung lesions

Opportunistic Forms. These are usually initiated a pulmonary disease in compromised hosts. Today, Cryptococcosis is the fourth most commonly recognized cause of life-threatening infection in AIDS patients.

Ø Pulmonary

Ø CNS / meningitic (This is the most diagnosed form of disease. Early presenting symptoms may include headache or fever. Brain may have multiple or single lesions and/or cryptococcal granulomas.)

Ø Cutaneous (rarely primary). Diagnosis based on pustular lesions or abscesses.

Ø Mucocutaneous. Diagnosis based on pustular lesions or abscesses.

Ø Osseous (bone involvement). Difficult to diagnose, but is indicated by X-ray & CT scan

Ø Visceral. Exrememly serious form of disease in organs or tissue. Diagnosis based on CT.


HIV infections

Chronic corticosteroid therapy

Organ transplants

Chronic leukemia and lymphomas

Sarcoidosis (an auto-immune disease)


Prompt diagnosis

Intensive treatment with Amphotericin B

Immunosuppressive regimen (for hig-risk patients)

Control of underlying disease


Spinal Tap

Increased presur due to fluid accumulation

Clear fluid (if disease is due to bacterial infection, fluid becomes clopudy)

Elevated cell count

Low sugar

Organisms sparc eor numerous

Latex Agglutination test or Indirect fluorescent antibody test used

CAT Scans & MRI also used, but not very helpful.









Coccidioomycois is a respiratory infection which usually resolves spontaneously but can become an acute/chronic/severe mycosis. It is caused by Coccidiodes immitis (a hyphomycete of the Fungi Imperfecti suspected to be a true Plectomycete of the onygenales order based on chitin synthase studies and 18S rDNA)

Recovery from the primary pulmonary form usually results in protective immunity.

Synonyms: Posada’s disease, Valley Feverl, San Joaquin Valley Fever, Valley Bumps, Desert Rhuematism.

This was the first "fatal mycosis" to be discovered to have mild and inapparent form.


Though there are no prepuberty sex differences with regard to infection or dissemination, in adults, males more likely to acquire disease which implies that hormones may play some role.

Dark-skinned persons are more afflicted and tend to develop the more serious forms.

Many AIDS patients test positive for coccidiodomycosis, but the rate of coccidiomycosis in AIDS patients in endemic areas is low.



In the host, the fungus forms spherules rather than mycelia. Multinucleate conidium. The spherule, which contains endospores, results from internal septation and eventually ruptures. Conidia are characterized as "winged conidia".

Hyphae break into enteroartric conidia – form arthroconidia.


Coccidioidin. This is obtained by extractions of polyvalent antigens from numerous strains.

Antigen 1 – involved in LPA and TP tests

Antigen 2 – involved in CF and ID test

Antigens 3 & 4 – significance not well established

Sperulins – extracts of formalin killed spherules


Ampho B (or Itraconazole) is commonly used to treat coccidiodomycosis.


Primary Coccidiodomycosis – Pulmonary (asymptomatic and symptomatic) and Cutaneous (rare) infections both result in protective immunity

Secondary Coccidiodomycosis

Ø Pulmonary (benign chronic III (cavitary or progresive)

Ø Disseminated (meningeal, chronic cutaneous or generalized)


Conidia or small spherules are phagocytosed and processed by macrophages, which display antigen to sensitize T-lymphocytes.

This results in cell mediated immunity & Dekayed type hypersensitivity response to the fungus

As more macrophages are stimulated, B cells produce IgM followed by IgG.



Chromoblastomycosis is a chronic localized granulomatous mycosis of the skin and subcutaneous tissue characterized by verrucoid, ulcerated, and crusted lesions that may be raised. It is caused exclusively by black fungi.

It may be caused by 4 (maybe 6) species (anamorphs) of dematiaceae of the Fungi Imperfecti: (These agents are also considered to by hyphomycetous molds)

Phialphora verrucosa

Fonsecae pedrosoi & F. compacta

Cladophialophora carrionii

Rhinocladiella aquaperma

These species usually exhibit tissue dimorphism characterized by the production of sclerotic bodies in subcutaneous granulomas; that is, they tend to form sclerotic bodies in host tissues rather than yeasts. These fungi grow as molds in vitro, but one can induce sclerotic bodies under acidic conditions (pH = 2.5). The formation of sclerotic bodies is probably a Ca2+ regulated process. If too much Ca2+ is added, the sclerotic bodies may revert back to hyphae.

Lesions are generally granulomatous and treatment usually involves major surgery or systemic antifungals.


Trauma or puncture wound at site of initial lesion

Initially small, raised erythemoid papule which is rarely pruritic.

Papules / pustules become violaceous and have modest cell infiltration.

Lesions become scaly. Fungi in lesions may be present as distorted hyphal elements as they become sclerotic bodies. (Altered morphology is more resistant to antifungal therapy due to thickening of cell wall and more melanin (which binds oxidative radicals).

Lesion may become raised and start to coelesce into cauliflower-like skin structures resulting form extensive granuloma formations in skin and subcutaneous fissures.

Invasion of new areas at slow, chronic rate. Mechanism of spread is unclear, but it is thought that fungi may be spread by phagocytic cells.


Observation of characteristic lesions

Observation of sclerotic bodies

Culture of fungus and identification by observing conidial structures

Serodiagnosis (poor)


Surgery (for early lesions), medical management or supportive therapy (for advanced cases), and antimycotics (as last resort)



Candidiasis is a primary or secondary infection involving a member of the form genus Candida, particularly C. albicans. (The form-genus Candida also includes C. tropicalis, C. parapsilosis, C. krusei, and C. glabrata. All Candidia species are asexual members of the Blastomycetes form-class of the Fungi Imperfecti and have suspected Hemiascomycotina affinities.)

Candiasis is general an opportunistic (secondary) infection. The extent of the disease ranges from mild to chronic and is rarely granulomatous. Many systemic forms are life threatening.

C. albicans represents the most common agent of mycosis.

More form-species of Candidia (and their teleomorph counterparts: Pichia, Lodderomyces, Kluyveromyces, etc.) have been shown to be involved in more infections than those associated with any other form-genus.

Many form-species are found on body surfaces as normal flora and live as commensals in harmony with the host. Problems arise when there is overgrowth of the fungi.


Though Candidiasis has been documented since antiquity as thrush, vaginal candidiasis, etc., in the 1940’s there was a rise in the number of opportunistic cases due to the rise in antibiotic use and other medical treatments. Since the 1980’s, the increase in the incidence of AIDS has also contributed to the number of opportunistic cases.

Newborns can acquire thrush from mothers with vaginal infections as they pass through the birth canal. Neonates are especially susceptible to infection since their resident flora have not yet been established. Incidence of newborn oral thrush varies with degree of maternal infection, maturity of the infant at birth, method of feeding (breast-fed babies have a greater likelihood of contracting thrush), and the social conditions.

Skin surveys show that Candida can be isolated form the skin surfaces of normal individuals.

Risk factors associated with crude mortality rate in hospital (such as UoI) are the number of antibiotics received prior to infection, isolate of Candida species from sites other than blood, prior hemodialysis, and Hickman catheterization. Patients treated with cancer chemo-therapeutic drugs or post-operative patients are at a higher risk if not treated immediately after detection of Candida in blood.

Candidia infection is prevalent in AIDS patients. As AIDS progresses and the CD4 lymphocyte population falls there is a progression towards pharangeal Candidiasis. Erythmatous and pseudomembranous oral candidiasis predict the progression of AIDS in HIV+ individuals.

Very few people actually die of candidiasis due to a very different immunology. Patients usually die because they are in the full-blown stage of AIDS or other disease.


Extreme youth. Especially in babies 3-5 days old who have not yet established resident flora.

Physiological changes. These include pregnancy (in which case there is an increae in the [glycogen]), steroids, onset of puberty, extremes in diet, drugs.

Prolonged antibiotics use.

General debility & the constitutionally inadequate patient.

Avitaminosis – correlation between low riboflavin (2) and candidiasis.

Diabetes – high blood glucose

Cancer and its therapy



Corticosteroid/steroid therapy

Iatrogenic and barrier break procedures. For example, burns, catheters, dialysis, surgery, injection, constant moisture, etc.


Candidiasis is due to overgrowth and infections which are symptomatic (?). There are three types of infections: mucotaneous, cutaneous, and systemic.

Mucotaneous. These are related particularly to youth, physiological change, and antibiotic use. Bronchial/pulmonary & alimentary infections are associated with AIDS (low CD4 count)

oral infections


bronchial/pulmonary infections

alimentary infections

chronic mucotaneous. These are condition of constitutionally inadequate patients (T-cell inadequate). Usually patients cannot contain the Candida on their skin and develop a mucotaneous mycosis. These are usually associated with children and the elderly.

Ø Cutaneous

1. Intertriginous (between fingers and toes) and Generalized (over whoel body)

2. Onychomycosis

3. Diaper disease

4. Candidal granuloma

Systemic. These are usually related to general debility and iatrogenic/barrier brak procedures.

1. Urinary tract

2. Endocarditis

3. Meningitis

4. Septicemia

Allergic reactions can also be launched against Candida.






Ø Superficial candidiasis. These are due to overgrowth of Candida species which remain localized to the skina nd subcutaneous tissues.

Cutaneous infection, chronic mucotaneous infection, onychomycosis, oropharangeal mycosis, vulvovaginitis, keratitis, conjunctivitis (an inflammations of the cornea and iris/ inflammation of the mebrane lining the eylids

Ø Deep candidiasis. This is usually die to local inoculation.

Esophagitis, gastrointestinial candidiasis, UTI (includes fungus ball of the ureter, cystitis, renal abcess, and pyelisis {inflammation of the plvis/kidney}), peritonitis/intra-abdominal abcess

Ø Hematogenously disseminated infections / Fungemia

Candidemia, chronic disseminated (hepatosplenic) candidiasis, supportive phlebitis (inflammation of vein), endocarditis, meningitis, endophthalmitis (inflammation of inside of the eye), arthritis, osteomyelitits.


Once it enters other sites, invasive Candida is much harder to treat than while it is in the bloodstream. This is because when fungi grow in the bloodstream they are generally found as yeast, which macrophages and PMNs can help control, but once they are in the tissues, fungi form mycelia, which are harder for the body to eliminate.

Host defenses include:

Ø Phagocytosis by PMNs and macrophages

Ø Defensins from granules in PMNs (granules kill fungus)

Ø Fungicidal agents excreted by monocytes and PMNs into the immediate yeast cell microenvironment

Ø A cytoplasmic 30-kD protein, which inhibits Candida albicans growth, is released by dying PMNs


Nystatin (mycosamine, dideoxy-3-amino mannose, a degenerate heptaene since it contains 6 double bonds) is the traditional drug of choice for "colonizing/superficial" candidiasis. It has been replaced mostly by azoles, triazoles, EBIs, etc.


1) All patients with blood culture for Candida should be treated with antifungal immediately.

2) Treatment should be with Amp. B until a nationally recommended drug is decided on.

3) Less serious cndidiais in patients with low potential for developing systemic candidiasis should be treated with fluconazole/nystatin.


Hematogenously-spread candidiasis is difficult to diagnose. Determining the kind of Candida involved is very difficult.

1) No reliable techniques available on wide-spread commercial basis.

2) Most helpful clues:

Positive blood culture

Ø Hematogenous Candida endopthalmitis

Ø Hematogenous Candida osteomyelitis (bone and bone marrow – associated infection; from CT)

Ø Candiduria in absence of instrumentation of the urinary tract

3) Yeast culture and identity


growth at 37*C

negative capsule in India ink preps

germ-tube formation in FCS. This is the "gold standard" for identification of C. albicans because most Candida form-species don’t produce germ-tube in FCS to the extent C. albicans does.

chlamydospore formation and/or sucrose assimilation


The germ-tube test is 95% accurate for the presumptive ID of C. albicans.

Small numbers of young test organism (from isolation in BHI or Sab) is inoculated in media (rabbit, FCS, or human serum). The ample is incubated at 37*C for 203 hours and then studied. If yeast cells with germ tubes are observed, the sample is probably C. albicans.

Germ-tubes are characteristic yeast cell structures of C. albicans. A septum forms between the mother cell and the germ-tube. This septum has a micropore and may also have woronin bodies.

VITEK is a system that can be used to ID and differentiate Candida.





Blastomycosis is a chronic granulomatous and supperative disease having a primary pulmonary stage frequently followed by dissemination to other body sites, particulary the skin and bone.

Caused by

Anamorph: Blastomyces dermatitidis (cleistothecial ascomycete – Plectomycete)

Telomorph: Ajellomyces dermatitidis (thermally dimorphic hyphomycete)

Synonyms: North American Blastomycosis, Gilchrists’ disease, Chicago dsease

Not considered opportunistic.

Resolution does not result in protective immunity.


Differences: Blatomycosis is. . .

caused by different species than histplasmosis

not opportunistic, does not appear to be self-limiting

resolution doesn’t generally result in protective immunity

blastomycosis tends to progress to active skin and bone lesions

not intracellular pathogen

resolution doesn’t leave lesions


Approx same endemic US location

Both caused by single species of Ajellomyces, which are closely related and heterothallic

Both initiated most often as primary pulmonary infection brought about by inhalation of conidia

Both caused by thermally dimorphic fungi

Both thought to be fatal before Ampho B


Ajellomyces dermatitidis (heteothallic, dimictic teleomorph)

Phylum - Ascomycota

Subphylum - Euascomycotina

Class - Plectomycetes (forms cleistothecia = ascocarp and has prototunicate asci)

Order - Onygenales (blastoconidium)

Family - Gymnoascaceae

Broad based buds are characteristic of tissue forms of Blastomycosis. Yeast cells tend to be multinucleate and have simple hyphal septum with Woronin bodies. Often have productive septum.

Chrysosporium is a type of holoblastic conidia of blastomycosis similar to the macro & microconidia of Histoplasmosis. Paddle shaped, thick-walled, holoblastic conidia accumulate lipids and glycogen. Yeast mother cell can form a hyphal bud (to avoid phagocytosis) or yeast cells.


Primary pulmonary – resolves spontaneously or disseminates. Due to inhalation of spores resulting in alveolitis with macrophage invasion. Generally, lung lesions resolve, but lesions appear at other sites.

Chroninc cutaneous

Generalized systemic

Single organ system

Inoculation blastomycosis (rare)


Blastomycosis is commonly found in older individuals, particularly males, which implies that here may be a hormonal relationship.


subcutaneous nodules or ulcerating lesions

usually occur on exposed areas

some cases show bone involvement

TREATMENT – Amphotericin B and/or itraconazole


CF – uses broken yeast cell a AG

ID – uses AG A (highly reliable)



Period of vegetative growth (colonization and substrate exploitation)

Period of asexual reproduction (anamorphic phase)

Period of sexual reproduction (teleomorphic phase)



allow for dissemination (Spores are made in large numbers that disperse easily.)

allow for rapid reproduction

allow for survival due to dormancy qualities


rapid identification and classification

source of inocula for human infection

source of inocula for conatamination


Conidia are spores formed by budding or conversion of existing hyphae. These are generally made by Basidiomycota, Ascomycota and the Fungi Imperfecti.

Ø Mitospores – chromosomal complement derived directly from mitosis

· Endogenous mitospores – encysted zoospores, of fungal-like protists or chytridiomycota, and sporangiospores, of zygomycota

· Exogenous mitospores – conidia, blastospores, teliospores, etc. of Ascomycota, Basidiomycota, and Fungi Imperfecti

Ø Meiospores – chromosomal complement derived from meiosis

· Endogenous Meiospores – ascospores of Ascomycota

· Exogenous meiospores – basidiospores of Basidiomycota

Ø Karyospores – chromosome complement derived form zygote nuclei

· Karyospores – zygospores of zygomycota, oospores of Oomycota, and resting sporagia of Chytridiomycota

· Chlamydospores – vegetative units that attain spore-like characteristics (dormancy qualities)



These fungi generally do not elicit a host cellular response in normal hosts, but may do so in compromised patients.

Their infections do not exhibit a pathology (no granulomatous cysts or other lesions)

The patient usually only becomes concerned for cosmetic reasons, not due to any discomfort.

They generally affect the stratum corneum layer of the skin and/or the hair

The superficial mycoses can be subcategorized based on whether they cause infection of the skin or cause infection of the hair. The fungi which cause infection of the stratum corneum include Malassezia furfur and Exophilia werneckii. The fungi which cause infection of the hair include Piedraia hortae and Trichosporon beigelii.


Taxonomy: Malassezia furfur is classified under the nonphlogenetic taxon Fungi Imperfecti and is of the form-species blastomycetes with suspected (hetero)basidiomycota affinity based on rDNA analysis. The most common synonym is Pitryospornum obiculare. It may represent up to 6 lip-dependent species in 4 sirovors. M. pachydermatitis is a non-lipodependent species. Within the host it can be found as enteroblastic budding yeast and as hyphae.

Pathology: Malassezia furfur is the causative agent of the skin condition pityriasis versicolor (Pityriasis is commonly, erroneously called tinea versicolor. This is improper because "tinea" is used to refer to dermatophytoses.) It may also cause seborrheic dermatitis, a disease of the skin and scalp due to entrance of the fungus into the sebacaus glands. In AIDS and other compromised patients, this may be difficult to cure.

History: in 1846, Eicksteadt described the disease and in 1847 Sluyter named the disease pityriasis versicolor. Neither of the two scientists tried to isolate the disease. In 1853, Robin renamed the disease tinea versicolor, believing it to have been caused by the fungus Microsporum furfur. In 1889, Bailon renamed the fungus Malassezia furfur since it could be proven that Microsporum was not the correct genus.

Diagnosis of Pityriasis versicolor:

nature and color of lesions depends on several factors

a. fawn to brown on Caucasians (variation according to color of patient)

b. degree of exposure of colonized areas to sunlight

c. severity and extent of colonization

Microscopic observation of yeasts and hyphae in KOH skin scale preps (specifically looking for enteroblastic phialidic yeasts).

Sometimes golden yellow fluorescence of lesion under Woods lamp can be observed

Culture of fungus may be necessary to determine lipophilicity

Treatment: Generally Nizerol cream or Nizoral pills (both of which contain ketoconazole) are used in addition to other azoles.


Taxonomy: This is a member of the Fungi Imperfecti of the form-class hyphomycetes with suspected Ascomycota (specifically Euascomycotina) affinity based on studies of septal structure. It is a melanized (meaning melanin can be found in its cell wall), which may contribute to pathology as a virulence factor. Within the host, it is commonly found as enteroblastic annellate yeast and hypha on the stratum corneum.

Pathology: Exophala werneckii is the causative agent of Tinea nigra (a.k.a. Tinea nigra palmaris, since it is commonly found on the palms of the hands). Disease is characterized by black to brown nonscaly lesions.

Diagnosis of Tinea nigra:

Nature and location of "lesions" is generally brown or black (though coloration varies with the color of the host) and it is frequently found on the palms.

Microscopic observation of yeasts and hyphae in KOH skin scale preps (specifically looking for enteroblastic annelidic yeasts).

Culture of brown to greenish-black yeasts that produce soft colonies which may become "fuzzy" due to conversion to the hypha. Hypha produce annelloconidia.

Treatment: Miconazole or ketoconazole cream.


Taxonomy: The teleomorph of this species is Piedraia hortae, the anamorph is Trichosporon hortae. (The teleomorph was the first phase observed.) This fungus has a melanized cell wall. It is classified as a loculoascomycete of the Ascomycota.

Pathology: When it causes infection, Piedraia hortae forms hard, black nodules (which are actually loculoascostroma containing asci) on scalp hair.

Treatment: oral and topical azoles and cutting of hair.


Taxonomy: Trichsporon beigelii is classified under Fungi Imperfecti, so Trichsporon beigelii is its anamorphic name. It is included in the blastomycete form-class, though (based on studies of septal structure and rDNA) it has suspected Basidiomycota affinity. Like Cryptococcus, it has a capsule.

Pathology: When it causes infection, Trichsporon beigelii form soft, white nodules (which are arthroconidiogenous) on the beard, axilla, or pubic hair. Hypha break holoarthric thalloconidia to disseminate. Recently, Trichsporonosis has been noted as an emerging disease of compromised hosts and can be manifested as systemic trichsporonosis and genital white piedra. One strain notable for developing resistance is Trichosporon asahii.

Treatment: oral and topical azoles and cutting of hair.



Polyene macrolide antibiotics

The major members of this class are Nystatin and Amphotericin B (amphiliposomes)

Ergosterol Biosynthesis-Inhibiting Antifungals

These include synthetic imidiazoles, triazoles, and related compounds. These treat various fungal infections by inhibiting demethylation of lanosterol so no ergosterol can be made. The major members of this family are:

Miconazole – found in micitin and used to treat Candida


Fluconazole – found in diflucan and can be used for maint. therapy


Terbinafine – in Lamisil



Ketoconazole, Fluconazole, & Itraconazole are oral drugs which are replacing Ampho B therapy in some cases.

Griseofulvin – used in human and veterinary medicine

5-Fluorocytosine – used often in combination with other antifungal drugs, especially Amphotericin B

KI – used for sporotrichosis

Glucan Sythase Inhibitors

These include Capso fungin and FK463



The subcutaneous mycoses are a heterogeneous collection of infections caused by a large variety of fungi and characterized by lesion development in the subcutaneous tissues usually at site of traumatic implantation.

These are primary pathogenic mycoses. Severity of disease is determined by the virulence of the fungus and the defenses of the host. Causative agents are usually fungi imperfecti and many are thought to be related based on studies of septal structures and DNA analysis. Any of the demitiaceous (melanized) agents are thought to be loculoascomycetes. Agents are soil saprophytes that tend to live of dead or dying plant materials and may or may not exhibit vegetative dimorphism of polymorphism, though some soma can form yeasts, molds, sclerotic bodies, etc. Infections are generally localize and chronic.

In normal hosts, the fungus spreads along the lymphatics, by self-inoculation, or by unknown mechanism (possibly phagocytic spread). In compromised hosts, the fungus may be spread hematogenously.


Chromoblastomycosis, caused by approximately 5 species.

Subcutaneous Phaeohyphomycosis, often caused by black fungi

Mycotic mycetoma, caused exclusively by black fungi

Subcutaneous Zygomycosis

Lobomycosis, caused by Loboa loboi

Sporotrichosis, caused exclusively by Sporothrix schenckii (a black fungus).


Dematomycoses are mycoses caused by black fungi.

Ø The dematiaceae are a form-family of the Fungi Imperfecti with members which include blastomycetes, hyphomycetes, and possibly also some coelomycetes. They form brown-black vegetative and reproductive structures due to deposition of melanin (via DHN pathway) in their cell walls.

Ø The dematiaceous fungi are also known as melanized black fungi and phaeoid fungi.

Ø DNA sequecing suggests that most are members of the chaetothyriomycetales order of loculoascomycetes.


Mycoses caused by dematiaceous (phaeoid) fungi:

Chromoblastomycosis (subcutaneous mycosis): Cladophialophora carrionii, Fonsecaea perdrosoi, Phialophora verrucosa

Cladosporosis (systemic mycosis): Cladophialophora bantiana

Dematiaceous (subcutaneous mycosis) Phaeohyphomycosis: Exophiala jeanselmei & Wangiella dermatitidis

Dematiatceous Mycetoma / Black Grain Mycetoma (subcutaneous mycosis): E. jeanselmei

Tinea Nigra (superficial mycosis): E.werneckii

Black Piedra (superficial mycosis): Piedraia hortae