Production of antimicrobial resistant spores by C. difficile and their dispersal in the environment facilitates the transmission of Clostridiodes difficile associated disease, especially in healthcare environments. The spores are resistant to common disinfectants and biocides, thus allowing them to withstand hospital cleaning regimes. If instead, a spore can be induced to germinate, it will be more sensitive to common antimicrobials and it may be readily eliminated by common disinfectants and biocides. Certain bile acids and co-germinants are known to initiate spore germination. It is hypothesised that a suitable surface-anchored bile acid derivative might be able to initiate germination in C. difficile spores. If this could be combined with an antimicrobial component, then there would be the possibility for a spore germination-extermination dual-action material that could potentially be deployed as antimicrobial surfaces in the clinical environment. Therefore, the aim of this project is to produce surfaces with attached bioactive entities that are able to initiate germination of C. difficile spores, and which also have general wide-spectrum antimicrobial properties. The Aston team has experience in the synthesis and screening of bile acid related germinants of the general type required. The chemistry is amenable to analogue synthesis for the optimisation of the material properties and the associated desired C. difficile germinant and antimicrobial activities. Such spore germination-extermination dual-action materials could be a useful weapon in the fight against microbial infection in the clinical setting. The major component of the project is synthetic organic chemistry, and this will be complemented by biological screening of the material produced.
References
• A Revised Understanding of Clostridioides difficile Spore Germination. Lawler, A., Lambert, P. & Worthington, T., 1 Sep 2020, In: Trends in Microbiology. 28, 9, p. 744-752 9
• Physical and chemical factors influencing the germination of Clostridium difficile spores, Wheeldon, L. J., Worthington, T., Hilton, A., Elliott, T. S. J. & Lambert, P. A., Dec 2008, In: Journal of Applied Microbiology. 105, 6, p. 2223-2230