Clostridium difficilevirulence factors: Insights into an anaerobic spore-forming pathogen

Abstract

The worldwide emergence of epidemic strains of Clostridium difficile linked to increased disease severity and mortality has resulted in greater research efforts toward determining the virulence factors and pathogenesis mechanisms used by this organism to cause disease. C. difficile is an opportunist pathogen that employs many factors to infect and damage the host, often with devastating consequences. This review will focus on the role of the 2 major virulence factors, toxin A (TcdA) and toxin B (TcdB), as well as the role of other putative virulence factors, such as binary toxin, in C. difficile-mediated infection. Consideration is given to the importance of spores in both the initiation of disease and disease recurrence and also to the role that surface proteins play in host interactions.

Clostridium difficile Infection

“…Both toxins (production and activity) and spores have been implicated in epidemicity 82,122,227 . However, strong evidence supporting this link is lacking and the ability of C. difficile to cause epidemics is likely to be a multifactorial process that involves a delicate balance of factors that affect virulence and transmissibility 74,75 . It should be noted that increased virulence might not correlate with transmissibility, which might be favoured when hosts remain relatively healthy 75 .…”

“…Regulation of expression-Although several virulence factors contribute to the retention of C. difficile within the gastrointestinal tract 74,75 , the symptoms of CDI correlate with the presence of a toxin-encoding pathogenicity locus (PaLoc) in the bacterial genome 76,77 . In most strains, the PaLoc is located at the same site in the chromosome 77,78 .…”

“…In most strains, the PaLoc is located at the same site in the chromosome 77,78 . The PaLoc in most pathogenic C. difficile strains encodes two large homologous toxins (TcdA and TcdB) and three proteins that seem to regulate toxin production and secretion (TcdR, TcdE and TcdC) 74,75,78 (FIG. 4a).…”

The complex factors that contribute to Clostridium difficile infection

“…This, in turn, leads to the loss of tight junction integrity in the gut, and movement of fluid into the intestinal lumen, causing diarrhoea 10 . Toxins A and B also induce inflammatory responses, which contribute to host tissue damage during infection 12,13 .…”

“…Once in the gut, germination occurs and the vegetative cell expresses factors required for survival and pathogenesis in the host 14 . C. difficile may produce a number of these factors, which include fibronectin-binding proteins, S-layer, capsule, type IV pili, and flagella 12,13 . Some strains also produce an additional toxin termed binary toxin, or CDT (C. difficile transferase).…”