Evidence for holin function of tcdE gene in the pathogenicity of Clostridium difficile

Toxigenic strains of Clostridium difficile produce two large bacterial toxi ns called toxins A (TcdA) and B (TcdB), tcdA and tcdB genes are located on the pathogenicity locus of C, difficile, a unique characteristic of toxigen ic strains of this species. Intergenic to the two toxin genes is tcdE, a sm all 501-bp open reading frame of unknown function. Expression of the tcdE g ene in Escherichia coli caused bacterial cell death. Computational analysis of the amino acid sequence of TcdE revealed structural features that are s trikingly similar to a class of bacteriophage proteins called holins, Holin s are cytolytic proteins that cause lysis of bacterial hosts to effect the release of progeny phages, Further analysis of the recombinant done express ing TcdE by transmission electron microscopy confirmed that the site of act ion of TcdE is on the bacterial cell membrane. The results provide evidence that TcdE is structurally and functionally similar to holin proteins, TcdE may function as a lytic protein to facilitate the release of TcdA and TcdB to the extracellular environment, as these toxins lack signal peptide.