Genomic analyses reveal two distinct lineages of Corynebacterium ulcerans strains

Abstract

Corynebacterium ulcerans is an important zoonotic pathogen which is causing diphtheria-like disease in humans globally. In this study, the genomes of three recently isolated C. ulcerans strains, 4940, 2590 and BR-AD 2649, respectively from an asymptomatic carrier, a patient with pharyngitis and a canine host, were sequenced to investigate their virulence potential. A comparative analysis was performed including the published genome sequences of 16 other C. ulcerans isolates. C. ulcerans strains belong to two lineages; 13 strains are grouped together in lineage 1, and six strains comprise lineage 2. Consistent with the zoonotic nature of C. ulcerans infections, isolates from both the human and canine hosts clustered in both the lineages. Most of the strains possessed spaDEF and spaBC gene clusters along with the virulence genes cpp, pld, cwlH, nanH, rpfI, tspA and vsp1. The gene encoding Shiga-like toxin was only present in one strain, and 11 strains carried the tox gene encoding the diphtheria-like toxin. However, none of strains 4940, 2590 and BR-AD 2649 carried any toxin genes. These strains varied in the number of prophages in their genomes, which suggests that they play an important role in introducing diversity in C. ulcerans. The pan-genomic analyses revealed a variation in the number of membrane-associated and secreted proteins that may contribute to the variation in pathogenicity among different strains.

The Genus Corynebacterium in the Genomic Era

“…Furthermore, variations between the transmembrane proteins and proteins secreted among the different species have been identified, contributing to the variability of the pathogenicity between them. This study made a greater understanding possible, regarding the knowledge around the virulence of this emerging pathogen [38].…”

Phylogenomic characterisation of a novel corynebacterial species pathogenic to animals

“…The key virulence factor among C. ulcerans strains is the tox gene (Sangal and Hoskisson 2014;Sangal et al 2014;Subedi et al 2018); which is borne by a corynephage (Sekizuka et al 2012) or pathogenicity island (Meinel et al 2014). However, non-toxigenic tox gene bearing (NTTB) C. ulcerans strains, where tox gene is a pseudogene, are also common (Dias et al 2011;Eisenberg et al 2014;Fuursted et al 2015;Wagner et al 2011;Zakikhany et al 2014).…”

“…However, non-toxigenic tox gene bearing (NTTB) C. ulcerans strains, where tox gene is a pseudogene, are also common (Dias et al 2011;Eisenberg et al 2014;Fuursted et al 2015;Wagner et al 2011;Zakikhany et al 2014). Other known virulence-associated genes in C. ulcerans include pld (phospholipase D), nanH (neuraminidase H), cp40 (corynebacterial protease), vsp1 and vsp2 (venom serine protease) and rbp (Sangal et al 2014;Sekizuka et al 2012;Subedi et al 2018;Trost et al 2011). The rbp gene encodes a ribosomal-binding protein that is similar to Shiga-like toxin and is only reported in C. ulcerans strain 809 (Subedi et al 2018;Trost et al 2011).…”

“…Other known virulence-associated genes in C. ulcerans include pld (phospholipase D), nanH (neuraminidase H), cp40 (corynebacterial protease), vsp1 and vsp2 (venom serine protease) and rbp (Sangal et al 2014;Sekizuka et al 2012;Subedi et al 2018;Trost et al 2011). The rbp gene encodes a ribosomal-binding protein that is similar to Shiga-like toxin and is only reported in C. ulcerans strain 809 (Subedi et al 2018;Trost et al 2011). Interestingly, an Rbp homolog was found in C. diphtheriae HC04 (Weerasekera et al 2019).…”

“…Two Spa gene clusters, spaDEF and spaBC, have been reported among C. ulcerans strains (Subedi et al 2018;Trost et al 2011). Pilus gene clusters encode surface pili that play a key role in adhesion and invasion to the host cells (Broadway et al 2013;Reardon-Robinson and Ton-That 2014).…”