Adhesion by Pathogenic Corynebacteria

Abstract

Pathogenic members of the genus Corynebacterium cause a wide range of serious infections in humans including diphtheria. Adhesion to host cells is a crucial step during infection. In Corynebacterium diphtheriae, adhesion is mediated primarily by filamentous structures called pili or fimbriae that are covalently attached to the bacterial cell wall. C. diphtheriae produces three distinct pilus structures, SpaA-, SpaD- and SpaH-type pili. Similar to other types, the prototype SpaA pilus consists of SpaA forming the pilus shaft and two minor pilins SpaB and SpaC located at the base and at the tip, respectively. The minor pilins SpaB/SpaC are critical for bacterial binding to human pharyngeal cells, and thus represent the major adhesins of corynebacteria. Like pili of many other gram-positive microbes, the assembly of corynebacterial pili occurs by a two-step mechanism, whereby pilins are covalently polymerized by a transpeptidase enzyme named pilin-specific sortase and the generated pilus polymer is subsequently anchored to the cell wall peptidoglycan via the base pilin by the housekeeping sortase or a non-polymerizing sortase. This chapter reviews the current knowledge of corynebacterial adhesion, with a specific focus on pilus structures, their assembly, and the mechanism of adhesion mediated by pili.

Pilus Gene Pool Variation and the Virulence of Corynebacterium diphtheriae Clinical Isolates during Infection of a Nematode

“…Consistent with this notion, while multiple pilus gene clusters are also detected in the genome of many toxigenic and nontoxigenic clinical isolates of C. diphtheriae, the SpaA pilus gene cluster was observed at high frequency (19). Remarkably, the SpaA pilus gene cluster was also shown to be more prevalent than the SpaD and SpaH gene clusters among different corynebacterial species (30). Interestingly, our analysis of the draft genome of C. diphtheriae bv.…”

“…Soon after the identification of C. diphtheriae (30), classic microbiologic experiments led to the discovery of the organism's potent disease-causing exotoxin, DT, which remained the major known virulence factor of this pathogen. The phenomenal success of diphtheria vaccines generated from the inactive DT has eclipsed the need to search for additional virulence factors that may contribute to the severity and complexity of the disease that once killed humans in major epidemic proportions.…”

Pangenomic Study of Corynebacterium diphtheriae That Provides Insights into the Genomic Diversity of Pathogenic Isolates from Cases of Classical Diphtheria, Endocarditis, and Pneumonia

“…Adhesive pili play pivotal roles in bacterial colonization, pathogenesis, and biofilm development (45). Pilus assembly in corynebacteria occurs by a two-step mechanism, whereby pilins are polymerized and then covalently anchored to cell wall peptidoglycan (62). In C. diphtheriae, a pilinspecific sortase catalyzes the polymerization of the pilus, consisting of the shaft protein, tip pilin, and base pilin (45).…”

Characterization of DIP0733, a multi-functional virulence factor of Corynebacterium diphtheriae

“…diphtheriae might be the best-investigated pathogenic member of the genus; however, even for this species only a few virulence factors have been characterized in detail. Beside the diphtheria toxin these include mainly pili and a few other adhesion factors (see Collier, 2001;Rogers et al, 2011;ReadonRobinson & Ton-That, 2013; for reviews), while little is known about the factors mediating the entry processes in the host cell and the receptors 3These authors contributed equally to this paper.…”