Genomic analysis of the erythromycin resistance element Tn5398 from Clostridium difficile

Clostridium difficile is a nosocomial pathogen that causes a range of chron ic intestinal diseases, usually as a result of antimicrobial therapy. Macro lide-lincosamide-streptogramin B (MLS) resistance in C difficile is encoded by the Erm B resistance determinant, which is thought to be located on a c onjugative transposon, Tn5398. The 9630 bp Tn5398 element has been cloned a nd completely sequenced and its insertion site determined. Analysis of the resultant data reveals that Tn5398 is not a classical conjugative transposo n but appears to be a mobilizable non-conjugative element. It does not carr y any transposase or site-specific recombinase genes, nor any genes likely to be involved in conjugation. Furthermore, using PCR analysis it has been shown that isolates of C. difficile obtained from different geographical lo cations exhibit heterogeneity in the genetic arrangement of both Tn5398 and their Erm B determinants. These results indicate that genetic exchange and recombination between these determinants occurs in the clinical and natura l environment.