Analysis of the pathogenicity locus in Clostridium difficile strains

The genes for Clostridium difficile toxins A and B (tcdA and tcdB) are part of a 19.6-kb pathogenicity locus (PaLoc) that includes the genes tcdD, tcd E, and tcdC. To determine whether the C. difficile PaLoc is a stable and co nserved genetic unit in toxigenic strains, a multiplex polymerase chain rea ction was used to analyze 50 toxigenic, 39 nontoxigenic, and 2 toxin-defect ive isolates. The respective amplicons were identified for tcdA-E in the to xigenic isolates; these were absent in the nontoxigenic isolates. C. diffic ile P-829 lacked at least a fragment of tcdD, tcdB, tcdE, and tcdC, but tcd A was present. C. difficile 8864 had deletions in the tcdA and tcdC genes. These data suggest that the PaLoc is highly stable in toxigenic C, difficil e, nontoxigenic isolates lack the unit, and isolates with a defective PaLoc can still cause clinical disease. Further studies are needed to define the role of individual genes in the pathogenesis of C. difficile-associated di arrhea.