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Vibrio cholerae is a
diverse species found in aquatic environments worldwide, and can be
classified according to serogroup and biotype. While many strains
are considered non-pathogenic environmental isolates, certain strains
are capable of causing the severe diarrheal disease known as
cholera. Although the first six pandemics were caused by
strains of the O1 serogroup and classical biotype, the 7th pandemic
(beginning in 1961) was caused by O1 strains of the El Tor biotype.
In 1992, strains of the O139 serogroup emerged as the cause of
epidemic disease, further demonstrating the ability of this bacterium
to evolve as a reemerging pathogen.
Pathogenic O1 and O139 strains contain known virulence
factors for colonization (TCP, toxin co-regulated pilus) and toxin
production (CTX, cholera toxin phage), and cause epidemic disease in
season patterns. A significant amount of sporadic disease is
caused by non-O1/non-O139 strains, however. While these strains
are easily isolated from environmental reservoirs, they do not usually
contain TCP and CTX, and therefore must colonize and cause disease by
other mechanisms.
The completion of the genomic sequence of 7th pandemic O1 El Tor strain
N16961 in 2000 facilitated the study of V. cholerae
at the genomic level. I developed a spotted microarray
representing the 3,885 ORFs defined by the sequencing project, and used
these arrays for comparative genomic studies. This resulted in the
identification of ORFs unique to seventh pandemic strains. Many
of these ORFs encode a number of hypothetical proteins, but others
potentially encode transcriptional regulators, proteins involved in
chemotaxis and DNA repair, a pilin and a phospholipase. Further
study will include understanding the expression pattern of these genes
and the analysis of the effect of gene deletions on pathogenic
potential, global gene expression and environmental survival. Other
studies in the laboratory focus on the identification of novel or
unique virulence factors which may have been acquired by
non-O1/non-O139 strains.
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Dziejman, M., D. Serruto, et al. "Genomic
characterization of non-O1, non-O139 Vibrio cholerae reveals genes for
a type III secretion system." Proc Natl Acad Sci U S A 102(9): 3465-70,
2005.
Larocque, R. C., J. B. Harris, et al. "Transcriptional profiling of
Vibrio cholerae recovered directly from patient specimens during early
and late stages of human infection." Infect Immun 73(8): 4488-93, 2005.
Faruque SM, Chowdhury N, Kamruzzaman M, Dziejman M, Rahman MH, Sack DA, Nair GB, Mekalanos JJ.
Genetic diversity and virulence potential of environmental Vibrio cholerae population in a cholera-endemic area.
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2123-8.
Bina J, Zhu J, Dziejman M, Faruque S, Calderwood S, Mekalanos J.
ToxR regulon of Vibrio cholerae and its expression in vibrios shed by cholera patients.
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2801-6.
Xu Q, Dziejman M, Mekalanos JJ.
Determination of the transcriptome of Vibrio cholerae during intraintestinal growth and midexponential phase in vitro.
Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1286-91.
Zhu J, Miller MB, Vance RE, Dziejman M, Bassler BL, Mekalanos JJ.
Quorum-sensing regulators control virulence gene expression in Vibrio cholerae.
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3129-34.
Dziejman M, Balon E, Boyd D, Fraser CM, Heidelberg JF, Mekalanos JJ.
Comparative genomic analysis of Vibrio cholerae: genes that correlate with cholera endemic and pandemic disease.
Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1556-61.
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