Inhibiting of Clostridium difficile spore germination by hypochlorous acid and SC5005

Abstract

Clostridium difficile is a Gram-positive obligate anaerobic spore-forming bacterium C difficile infection (CDI) which initiated by infection with the spore is the most frequent nosocomial infectious diarrhea Spores exposure and spore germination in the gut are the most important steps of CDI The C difficile spores are resistant to alcohol Another disinfectant hypochlorous acid (HOCl) has been shown bactericidal activity with several species including Escherichia coli Pseudomonas aeruginosa Staphylococcus aureus and C difficile In addition a sorabenib-based small compound SC5005 has been shown to suppress methicillin-resistant S aureus (MRSA) and C difficile Here we further characterized the effects of HOCl disinfectant and the small compound SC5005 on C difficile spores At first we found that HOCl has the potential to inhibit C difficile spore germination and the bacterial growth in a dose-dependent manner We showed that HOCl inhibits C difficile spore germination by damaging ultrastructure of spore Nevertheless this inhibition of spore germination was blocked by organics We demonstrated that HOCl can suppress C difficile spores on difference surfaces suggesting it has the potential to be an ideal anti-C difficile sporicidal agent for health care Second we found SC5005 also has the ability to inhibit taurocholate-mediated germination but in a competitive inhibition mechanism We demonstrated that SC5005 prevents CDI disease progression on CDI-mice animal model These results suggest that SC5005 has the potential to be an alternative strategy to prevent C difficile infection

Date of Award	2016 Aug 30
Original language	English
Supervisor	Pei-Jane Tsai (Supervisor)