Exploiting pathogens – Identification of a possible antimicrobial small molecule produced by Clostridium difficile

This project aims to characterise this potential C. difficile molecule to assess its viability as a new antimicrobial compound. To identify whether the genes within this C. difficile cluster are expressed, their transcription levels will be assessed by RT-PCR in physiologically relevant conditions, including in sessile communities in co-culture with commensal bacteria or human gut cells. Should the cluster be poorly expressed during these conditions, expression will be induced through either the creation of mutants of regulatory genes in the biosynthetic gene cluster or via promoter replacement. Genes responsible for production of the small molecule will then be mutated. Identification of the antimicrobial-like small molecule will be achieved through the direct analysis of the bacterial supernatant, using a range of comparative metabolic profiling techniques including: chromatography and mass spectrometry.

Finally the antimicrobial properties of the small molecule will be tested on a range of other pathogenic bacteria available in our lab including methicillin- resistant Staphylococcus aureus.

I studied for a BSc. (Hons) in Genetics at the University of the West of England (Bristol) between 2008 and 2011. I completed my final year project working on the bacterium Pseudomonas syringae in the laboratory of Dr Dawn Arnold, gaining a second author publication from his work. After briefly leaving science to pursue a career in teaching, I am now completing his PhD, studying the role of the enzyme LuxS during biofilm development of Clostridioides difficile.