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Stephen Calderwood
Department of Medicine
Massachusetts General Hospital
Infectious Disease Division
Gray Building, 5th Floor
55 Fruit Street
Boston, MA 02114
Tel: (617) 726-3811 Fax: (617) 726-7416
Email: calderwood.stephen@mgh.harvard.edu
4 postdoctoral fellows
We are interested in the genes and gene products involved in the
molecular pathogenesis of bacterial diarrhea caused by
gram-negative pathogens, particularly Vibrio cholerae,
Shigella, and enterohemorrhagic E. coli (EHEC), and
the regulation of these genes in response to environmental
stimuli. Recent work has included (1) use of the transposon
vector TnphoA to identify iron-regulated genes in V.
cholerae, including several important in virulence; (2)
demonstration that iron regulation of one of these V. cholerae
genes, irgA, is both negatively regulated at the
transcriptional level by a repressor protein (Fur) and positively
regulated by an upstream transcriptional activator, IrgB; (3)
cloning, sequencing and characterization of the V. cholerae
fur gene; (4) mutational and biophysical characterization
of V. cholerae Fur protein; (5) development of live,
attenuated V. cholerae vaccine strains to deliver
heterologous antigens to the common mucosal immune system; and
(6) investigation of two new regulatory genes in V. cholerae
that control expression of the ToxR regulon in response to
environmental signals and undergo phase variation.
Selected Recent References:
Watnick PI, Eto T, Takahashi H, Calderwood SB. Purification of Vibrio
cholerae Fur and estimation of its intracellular
concentration by antibody sandwich enzyme-linked immunosorbent
assay. J Bacteriol 1997; 179:243-247.
Ryan ET, Butterton JR, Smith RN, Carroll PA, Crean TI, Calderwood
SB. Protective immunity against Clostridium difficile
toxin A induced by oral immunization with a live, attenuated Vibrio
cholerae vector strain. Infect Immun 1997; 65:2941-2949.
Carroll PA, Tashima KT, Rogers MB, DiRita VJ, Calderwood SB.
Phase variation in tcpH modulates expression of the ToxR
regulon in Vibrio cholerae. Mol Microbiol 1997;
25:1099-1111.
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