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J. Med. Microbiol. -- Vol. 50 (2001), 613-619
© 2001 Society for General Microbiology
ISSN 0022-2615

BACTERIAL PATHOGENICITY

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

KAI SOO TAN, BOON YU WEE and KEANG PENG SONG

Program in Infectious Diseases, Department of Microbiology, Faculty of Medicine, National University of Singapore, Singapore

Corresponding author: Dr K.P. Song (e-mail: micskp{at}nus.edu.sg).

Received 23 Aug. 2000; revised version accepted 11 Dec. 2000.

Abstract

Toxigenic strains of Clostridium difficile produce two large bacterial toxins called toxins A (TcdA) and B (TcdB). tcdA and tcdB genes are located on the pathogenicity locus of C. difficile, a unique characteristic of toxigenic strains of this species. Intergenic to the two toxin genes is tcdE, a small 501-bp open reading frame of unknown function. Expression of the tcdE gene in Escherichia coli caused bacterial cell death. Computational analysis of the amino acid sequence of TcdE revealed structural features that are strikingly similar to a class of bacteriophage proteins called holins. Holins are cytolytic proteins that cause lysis of bacterial hosts to effect the release of progeny phages. Further analysis of the recombinant clone expressing TcdE by transmission electron microscopy confirmed that the site of action 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.




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