Identification of novel antimicrobials to target Clostridioides difficile.

Lisa Dawson (primary)
Infection Biology
Rivka Isaacson (secondary)


C. difficile is a disease of dysbiosis. The use of broad-spectrum antibiotics has resulted in a significant increase in both community and nosocomial C. difficile infection (CDI). There is a pressing urgency for novel anti-CDI therapy, given the high rate of treatment failure and relapse of CDI. We show that p-cresol produced by C. difficile has a deleterious effect on microbial diversity of the gut and provides C. difficile with a competitive advantage, particularly during relapse. Here we will assess small molecule inhibitors to prevent production of p-cresol and assess the effects on the C. difficile infection and the microbiome.


Passmore, I. J., M. P. M. Letertre, M. D. Preston, I. Bianconi, M. A. Harrison, F. Nasher, H. Kaur, H. A. Hong, S. D. Baines, S. M. Cutting, J. R. Swann, B. W. Wren and L. F. Dawson (2018). “Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria.” PLOS Pathogens 14(9): e1007191.

Dawson, L. F., E. H. Donahue, S. T. Cartman, R. H. Barton, J. Bundy, R. McNerney, N. P. Minton and B. W. Wren (2011). “The analysis of para-cresol production and tolerance in Clostridium difficile 027 and 012 strains.” BMC Microbiol 11: 86.

Harrison, M. A., A. Faulds-Pain, H. Kaur, B. Dupuy, A. O. Henriques, I. Martin-Verstraete, B. W. Wren and L. F. Dawson (2020). “Clostridioides difficile para-Cresol Production Is Induced by the Precursor para-Hydroxyphenylacetate.” J Bacteriol 202(18).

Martínez-Lumbreras, S., Alfano, C., Evans, N.J., Collins, K.M., Flanagan, K., Atkinson, R.A., Krysztofinska, E.M., Vydyanath, A., Jackter, J., Fixon-Owoo, S., Camp, A.H. & Isaacson, R.L. (2018) Structural and functional insights into B. subtilis sigma factor inhibitor, CsfB. Structure 26(4):640-648.

Molecules, cells and industrial biotechnology
Area of Biology
MicrobiologyStructural Biology
Techniques & Approaches
BiochemistryBioinformaticsBiophysicsGeneticsMicroscopy / ElectrophysiologyMolecular BiologySimulation / Modelling