Clostridium difficile endolysin therapeutic developments

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Clostridium difficile causes nosocomial disease with recently increased incidence and severity. Disease follows disruption of the normal GI tract microbiota, often following antibiotic treatment, emphasising the need to better target the pathogen without causing collateral damage to protective commensal species. We exploited the precise targeting of a bacteriophage endolysin (CD27L) derived from a C. difficile temperate bacteriophage to create a highly specific antimicrobial agent. CD27L has a very broad activity against C. difficile strains including ribotype027. GI tract commensal species and most other clostridia are insensitive. We propose to use recombinant lactic acid bacteria that express and release CD27L to overcome the challenges of GI tract delivery.

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