Pathogenicity Locus Plasmid PCS1-1 Encodes a Novel Clostridial Conjugation Locus

A major virulence factor in -mediated infection is the toxin TcsL, which is encoded within a region of the genome called the pathogenicity locus (PaLoc). 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 erythromycin resistance gene, conjugative transfer into a recipient isolate, R28058, was demonstrated. Bioinformatic analysis of pCS1-1 identified a novel conjugation gene cluster defined as the transfer () locus. Interruption of genes within the locus resulted in loss of pCS1-1 transfer, which was restored upon complementation in These studies provided clear evidence that genes within the locus are essential for the conjugative transfer of pCS1-1. The locus is present on all pCS1 subtypes, and homologous loci were identified on toxin-encoding plasmids from and and also carried within genomes of 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. is a bacterial pathogen that causes severe infections in humans and animals, with high mortality rates. While the pathogenesis of 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 gene to undergo conjugative transfer between distantly related strains of , which has far-reaching implications for the ability of to acquire the capacity to cause disease. Plasmids that carry 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.