Affiliation:
1. Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, Australia
2. Victorian Bioinformatics Consortium, Monash University, Clayton, Victoria, Australia
3. Department of Life Sciences, Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom
Abstract
ABSTRACT
A major virulence factor in
Clostridium sordellii
-mediated infection is the toxin TcsL, which is encoded within a region of the genome called the pathogenicity locus (PaLoc).
C. sordellii
isolates carry the PaLoc on the pCS1 family of plasmids, of which there are four characterized members. Here, we determined the potential mobility of pCS1 plasmids and characterized a fifth unique pCS1 member. Using a derivative of the pCS1-1 plasmid from strain ATCC 9714 which had been marked with the
ermB
erythromycin resistance gene, conjugative transfer into a recipient
C. sordellii
isolate, R28058, was demonstrated. Bioinformatic analysis of pCS1-1 identified a novel conjugation gene cluster defined as the
C. sordellii
transfer (
cst
) locus. Interruption of genes within the
cst
locus resulted in loss of pCS1-1 transfer, which was restored upon complementation in
trans
. These studies provided clear evidence that genes within the
cst
locus are essential for the conjugative transfer of pCS1-1. The
cst
locus is present on all pCS1 subtypes, and homologous loci were identified on toxin-encoding plasmids from
Clostridium perfringens
and
Clostridium botulinum
and also carried within genomes of
Clostridium difficile
isolates, indicating that it is a widespread clostridial conjugation locus. The results of this study have broad implications for the dissemination of toxin genes and, potentially, antibiotic resistance genes among members of a diverse range of clostridial pathogens, providing these microorganisms with a survival advantage within the infected host.
IMPORTANCE
C. sordellii
is a bacterial pathogen that causes severe infections in humans and animals, with high mortality rates. While the pathogenesis of
C. sordellii
infections is not well understood, it is known that the toxin TcsL is an important virulence factor. Here, we have shown the ability of a plasmid carrying the
tcsL
gene to undergo conjugative transfer between distantly related strains of
C. sordellii
, which has far-reaching implications for the ability of
C. sordellii
to acquire the capacity to cause disease. Plasmids that carry
tcsL
encode a previously uncharacterized conjugation locus, and individual genes within this locus were shown to be required for conjugative transfer. Furthermore, homologues on toxin plasmids from other clostridial species were identified, indicating that this region represents a novel clostridial conjugation locus. The results of this study have broad implications for the dissemination of virulence genes among members of a diverse range of clostridial pathogens.
Funder
Australian Research Council
Publisher
American Society for Microbiology
Cited by
16 articles.
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