Clostridium sordellii Pathogenicity Locus Plasmid pCS1-1 Encodes a Novel Clostridial Conjugation Locus

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.

In silico Identification of Novel Toxin Homologs and Associated Mobile Genetic Elements in Clostridium perfringens

“…A single strain can encode up to four different toxin plasmids, with a single plasmid encoding up to three toxin genes [2,3,7]. C. perfringens encodes two different classes of large plasmids, pCP13 and pCW3 [3,13,27], both of which have been demonstrated to be conjugative [27,28,29]. This study has identified six new plasmids, two pCP13-backbone plasmids and four pCW3 backbone plasmids.…”

Bacteriemia por Clostridium sordellii en paciente con neoplasia gastrointestinal. Reporte de caso y revisión de literatura

“…El 63% de los casos se presentaron en mujeres, 35% se asociaron con el parto normal, 22% con abortos inducidos médicamente, 9% con aborto espontaneo; el 37% de los casos se presentaron en hombres y se asociaron con procedimientos quirúrgicos o traumatismos en tejidos blandos, 42% son de origen no ginecológico y de dichos casos el 100% fueron mortales. Solo dos de los pacientes estaban infectados exclusivamente con C. sordellii [6][7][8][9] .…”

“…Las toxinas más estudiadas son las citotoxinas de gran peso molecular denominadas, toxina letal (LT) y toxina hemorrágica (HT), principalmente relacionadas con edema, necrosis y choque de rápida instauración. Ambas tienen algunas similitudes antigénicas y fisiopatológicas con las toxinas C. difficile A y B [9][10][11][12] . La LT inhibe la función del receptor de glucocorticoides, bloqueando la supresión sobre el factor de necrosis tumoral alfa.…”

A Highly Specific Holin-Mediated Mechanism Facilitates the Secretion of Lethal Toxin TcsL in Paeniclostridium sordellii

“…Mutagenesis using the TargeTron system and subsequent complementation was performed using a published method [55]. For mutagenesis, group II intron was retargeted to insert at the following distances from the predicted start of the coding sequence: between 161/162 bp of the anti-sense strand for ATCC 9714 tcsE, based on predictions from the Perutka Algorithm [56] via the ClosTron [57] design tool (http://clostron.com/clostron2.php, accessed on 10 March 2017).…”