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

Abstract

Clostridium perfringens causes a wide range of diseases in a variety of hosts, due to the production of a diverse set of toxins and extracellular enzymes. The C. perfringens toxins play an important role in pathogenesis, such that the presence and absence of the toxins is used as a typing scheme for the species. In recent years, several new toxins have been discovered that have been shown to be essential or highly correlated to diseases; these include binary enterotoxin (BecAB), NetB and NetF. In the current study, genome sequence analysis of C. perfringens isolates from diverse sources revealed several putative novel toxin homologs, some of which appeared to be associated with potential mobile genetic elements, including transposons and plasmids. Four novel toxin homologs encoding proteins related to the pore-forming Leukocidin/Hemolysin family were found in type A and G isolates. Two novel toxin homologs encoding proteins related to the epsilon aerolysin-like toxin family were identified in Type A and F isolates from humans, contaminated food and turkeys. A novel set of proteins related to clostridial binary toxins was also identified. While phenotypic characterisation is required before any of these homologs can be established as functional toxins, the in silico identification of these novel homologs on mobile genetic elements suggests the potential toxin reservoir of C. perfringens may be much larger than previously thought.

Analysis of the complete genome sequences of Clostridium perfringens strains harbouring the binary enterotoxin BEC gene and comparative genomics of pCP13-like family plasmids

“…The pCW3-like family is another family of conjugative C. perfringens plasmids that carry the tcp locus, and these plasmids are known to be disseminated among C. perfringens clades [ 20 , 34 ]. In contrast, the distribution of pCP13-like family plasmids has not been investigated, and only a limited number of pCP13-like family member plasmids, including pCP13 from strain 13, pCPNY83906550–1 from strain NY83906550, pCPT1 from strain T1, and p1 from strain JXJA17 (Table S 7 ) have been previously known [ 22 , 24 , 27 , 35 ].…”

Comparative in silico genome analysis of Clostridium perfringens unravels stable phylogroups with different genome characteristics and pathogenic potential

“…Recently, Lacey et al 2019 55 described eight novel toxin gene homologs that were associated with mobile elements in C. perfringens. Three of these genes were found in the data set under study; the edpA gene encoding a homolog with an epsilon toxin-like aerolysin domain (n = 1 strain), and ldpA (n = 1 strain) and ldpB (n = 2 strain) with a leucocidin/hemolysin domain (Fig.…”

Pathogenicity and virulence of Clostridium perfringens

“…Analyses of the 240 publicly available complete or draft C. perfringens genomes, along with unassembled short read sequences, revealed the presence of multiple putative novel toxin homologs with amino acid sequence identity to well-characterized C. perfringens toxins such as CPE, CPB, ETX, and ITX [ 116 ]. Those observations suggest that more genetic plasticity and virulence protein diversity remains to be identified in this bacterium.…”