Affiliation:
1. Howard Hughes Medical Institute and Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111
Abstract
ABSTRACT
The genes encoding cholera toxin (
ctxA
and
ctxB
) are encoded in the genome of CTXφ, a filamentous phage that infects
Vibrio cholerae
. To study the evolutionary history of CTXφ, we examined genome diversity in CTXφs derived from a variety of epidemic and nonepidemic
Vibrio
sp. natural isolates. Among these were three
V. cholerae
strains that contained CTX prophage sequences but not the
ctxA
and
ctxB
genes. These prophages each gave rise to a plasmid form whose genomic organization was very similar to that of the CTXφ replicative form, with the exception of missing
ctxAB
. Sequence analysis of these three plasmids revealed that they lacked the upstream control region normally found 5′ of
ctxA
, as well as the
ctxAB
promoter region and coding sequences. These findings are consistent with the hypothesis that a CTXφ precursor that lacked
ctxAB
simultaneously acquired the toxin genes and their regulatory sequences. To assess the evolutionary relationships among additional CTXφs, two CTXφ-encoded genes,
orfU
and
zot
, were sequenced from 13
V. cholerae
and 4
V. mimicus
isolates. Comparative nucleotide sequence analyses revealed that the CTXφs derived from classical and El Tor
V. cholerae
isolates comprise two distinct lineages within otherwise nearly identical chromosomal backgrounds (based on
mdh
sequences). These findings suggest that nontoxigenic precursors of the two
V. cholerae
O1 biotypes independently acquired distinct CTXφs.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
77 articles.
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