Our research - a brief summary
What can you tell me
about your subject of study, Wangiella dermatitidis?
What is phaeohyphomycosis?
layman's terms, why is your research important?
My laboratory uses the
so-called black yeast Wangiella dermatitidis (also know
as Exophiala dermatitidis) as a model
to discover cell wall-related virulence factors among
the more than 100 black fungi known to cause human
disease. The importance of our studies relates to the
knowledge that fungi blackened by the polymerization
of dihydroxynaphthalene (DHN) into melanin (DHN-melanin)
in their cell walls are among those most resistant to
current strategies of antifungal chemotherapeutic
intervention. Therefore, the discovery of critical,
but vulnerable, steps leading to the synthesis of DHN-melanin
and other cell wall components in our model should
identify excellent potential targets for the design of
antifungal therapeutic agents. These compounds should be useful
not only for the treatment of infections caused by
black fungi, but also other less resistant but more
Over the years, members of my
research groups have carried out a variety of studies
of Wangiella using techniques of cell biology,
genetics, physiology and biochemistry aimed at
establishing this fungus as a model. However,
during the last decade, my group has mostly been
engaged in cloning and studying genes and their
encoded products, which are involved in its cell wall biosynthesis.
For this purpose, we are using a variety of newly developed transformation,
gene disruption, and gene expression strategies. The
focus of these studies has been toward a molecular
genetic analysis of the relevance of chitin and
melanin biosynthesis to virulence, and of genes that
affect the extent and location of their cell wall
deposition. Although progress has been made in all
these areas, most has involved the
synthase (WdCHS) structural genes we have
identified. Because chitin biosynthesis per se does
not occur in vertebrates or mammals, the essential
multiple processes leading to the chitin synthesis are
considered to be important potential targets for drug
Our results to date
suggest that: i) no single chitin synthase (WdChsp: an
enzyme that polymerize chitin)
is required viability and growth of
W. dermatitidis at 25oC; ii)
of its five chitin chitin synthases, WdChs5p
contributes most directly to virulence,
probably because this isozyme is required for
sustained growth at infection temperatures (37oC);
iii) WdChs1p and
WdChs2p also contribute to virulence, because at least
one of these two isozymes is required with WdChs5 for
viability at 37oC; iv) WdChs3p likewise contributes to virulence
WdChs2p, because at least one of these two isozymes is
required with WdChs5p for virulence in our mouse
models. Currently we are attempting to
discover the regulatory mechanisms that control the
specific functions of these zymogenic enzymes, which allow them to
contribute to virulence in association with melanin
and in the different growth forms of Wangiella
expressed in human tissues.
What can you tell me about your subject of study,
dermatitidis, also often called Exophiala dermatitidis, is a so-called dematiaceous fungus that causes a variety of infections known collectively as
"phaeohyphomycosis". It is a species in the form-phylum Fungi
Imperfecti (Deuteromycetes), which means it has no known sexual
cycle, although a wealth of data strongly suggest it is
a member of the fungal phylum Ascomycota. What distinguishes it as
dematiaceous is the
black pigment (a type of melanin) that is in the cell walls of all its
different cell types. Wangiella is also a polymorphic organism,
which means that it exists in a variety of cell forms. These include its most common
type and the less common "sclerotic" cell,
hypha, true hypha, and conidium (spore) cell types. It the
laboratory it is grown mostly as a yeast in rich liquid medium, but
can be induced to convert to other forms by modifying growth conditions.
Wangiella is not readily found in the environments
but has been isolated worldwide. Although
ubiquitous, it causes only relatively few mycoses (fungal diseases),
Nontheless some reported cases have been very serious and
have resulted in patient death.
In vivo phenotypes of
Wangiella dermatitidis (L).
Colony of Wangiella
dermatitidis on rich medium
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What is phaeohyphomycosis?
Phaeohyphomycosis is a
term that was created in 1974 to include several
infections that are caused by many but not all
mycotic diseases caused by black fungi.
Phaeohyphomycosis can be superficial (on the surface
of the skin, hair, or nails), cutaneous (involving the
skin immediately below the outer epidermis),
subcutaneous (involving fatty tissue, connective
tissue, or muscle tissue), or systemic (involving the
circulatory and/or lymphatic system). The more
serious life-threatening, systemic phaeohyphomycoses,
mostly occurs with immunosuppressed individuals.
Although phaeohyphomycosis traditionally has been most
associated with dermotrophic forms of disease,
emerging systemic forms are being detected in
increasing number. For example, predisposing
factors for systemic infections with W.
dermatitidis include cystic fibrosis, lymphocytic
leukemia, diabetes mellitus, bronchiectasis,
rheumatoid arthritis and catherization.
For more information on
the clinical aspect of this topic, see Matsumoto,
T., Matsuda, T., McGinnis, M.R., and Ajello, L.
1992. Clinical and mycological spectra of
Wangiella dermatitidis infections.
Mycoses 36: 145-155.
Ungual phaeohyphomycosis (L),
Cutaneous phaeohyphomycosis (R).
courtesy of Dr. Tadahiko Matsumoto, Dept. of
Dermatology, Toshiba Hospital, 6-3-22 Higashi-oi,
Shinagawa-ku, Tokyo 140, Japan
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I'm not a scientist! Can you translate any of
this for me?
dermatitidis, the subject of this lab's
research, is a black (melanized) fungus.
Fungi (the plural of fungus) are a kingdom of
organisms that include your garden variety mushroom
(Agaricus brunnescens), baker's yeast (Saccharomyces
cerevisiae), the causative agents of
athlete's foot (E. floccosum, T. mentagrophytes,
and T. rubrum), the cause of yeast
infections (Candida albicans),
the mold you might see growing on your bread or
cheese (Rhizopus stolnifer), or the mold (Penicillium
notatum) that produces the medicine used to
combat an infection. Most people are
unaware of all the roles(both positive and negative)
that fungi play in our lives.
Wangiella has been known to cause disease that
can exhibit a wide variety of symptoms.
Although it can certainly be life-threatening, that
in itself is not the only reason for researching
this organism. Fungi have many common attributes
with "higher" life forms. Many
biochemical and molecular properties of cell growth
and regulation are similar. Thus, fungi like
Wangiella can be used as models to investigate
fungi and other life forms that are not as easily
studied at biochemical and molecular levels.
Wangiella has been demonstrated to be a
paradigm for mycotic infections caused by black
fungi. This means that it alone elicits all
the broad varieties of disease manifestations in
humans which are characteristic of those presented
by any other melanized fungus.. Understanding
the mechanisms that control the growth of these
fungi will provide insights into their pathogenicity
and virulence and may lead to improved treatments.