Toxin A-negative, toxin B-positive Clostridium difficile

Abstract

Clostridium difficile is a major cause of infectious diarrhea in hospitalized patients. Many pathogenic strains of Clostridium difficile produce two toxins TcdA and TcdB, both of which are pro-inflammatory and enterotoxic in human intestine. Clinically relevant toxin A-negative, toxin B-positive (A(-)B(+)) strains of Clostridium difficile that cause diarrhea and colitis in humans have been isolated with increasing frequency worldwide. This perspective describes these important toxin variant strains and highlights the need to use Clostridium difficile diagnostic methods that can detect both TcdA and TcdB.

Clostridium difficile infection: Early history, diagnosis and molecular strain typing methods

“…Toxin B does not cause fluid accumulation but is extremely cytopathic for tissuecultured cells [130]. These toxins are encoded by two genes, tcdA and tcdB, mapping to a 19.6 kb pathogenicity locus (PaLoc) and containing 3 additional regulatory genes, tcdC, tcdR, and tcdE, that are responsible for the synthesis and regulation of toxins A and B [135]. Deletions, insertions, or polymorphic restriction sites in one or more of the PaLoc genes can result in toxin variant strains that produce either toxin A or toxin B [135].…”

A chimeric protein comprising the glucosyltransferase and cysteine proteinase domains of toxin B and the receptor binding domain of toxin A induces protective immunity againstClostridium difficileinfection in mice and hamsters

“…12 It was initially reported that anti-TcdA antibodies were sufficient to protect the host against CDI. 13,14 However, recent studies demonstrated an even more important role of TcdB in the pathogenesis of CDI, [15][16][17][18] suggesting that an effective vaccine should target both toxins.…”

Protective antibody responses againstClostridium difficileelicited by a DNA vaccine expressing the enzymatic domain of toxin B

“…25 There are fewer reports on vaccine development based on toxin B and there is even less information on whether other regions of C. difficile toxins can also serve as protective antigens. With recent findings that toxin B is essential for virulence of C. difficile 6 and the fact that naturally occurring A-B+ strains exist and may cause clinical C. difficile infection, 26,27 it is now important to identify novel region(s) on toxin B antigens that can maximize the protective efficacy of C. difficile vaccines. In the current study, we used the DNA vaccination approach as a tool to screen the immunogenicity of various toxin A and toxin B fragments.…”