Both, toxin A and toxin B, are important in Clostridium difficile infection

Abstract

The bacterium Clostridium difficile is the leading cause of healthcare associated diarrhoea in the developed world and thus presents a major financial burden. The main virulence factors of C. difficile are two large toxins, A and B. Over the years there has been some debate over the respective roles and importance of these two toxins. To address this, we recently constructed stable toxin mutants of C. difficile and found that they were virulent if either toxin A or toxin B was functional. This underlined the importance of each toxin and the necessity to consider both when developing countermeasures against Clostridium difficile infection (CDI). In this article we discuss our findings in the context of previous work and outline some of the challenges which face the field as a result.

Figure 1

The pathogenicity locus (PaLoc) of Clostridium difficile 630, comprising the two toxin genes tcdA and tcdB as well as three ancillary genes, tcdR, tcdE and tcdC.

Figure 2

Survival curves showing the days from challenging hamsters with C. difficile spores to endpoint. Groups of 8 hamsters were infected with the respective strains, comprising the wild type (A⁺B⁺), the single toxin mutants (A⁺B⁻ and A⁻B⁺) and the double mutant (A⁻B⁻).