RESEARCH ARTICLE Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria Ian J. Passmore1, Marine P. M. Letertre2, Mark D. Preston3, Irene Bianconi4, Mark A. Harrison1, Fauzy Nasher1, Harparkash Kaur1, Huynh A. Hong4, Simon D. Baines5, Simon M. Cutting4, Jonathan R. Swann2, Brendan W. Wren1, Lisa F. Dawson1* 1 Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom, 2 Department of Surgery & Cancer, Imperial College London, London, United Kingdom, a1111111111 3 Bioinformatics and Next Generation sequencing core facility, National Institute for Biological Standards and a1111111111 Control South Mimms, Potters Bar, United Kingdom, 4 Department of Biomedical Sciences, Royal Holloway a1111111111 University of London, Egham, United Kingdom, 5 Department of Biological and Environmental Sciences, a1111111111 University of Hertfordshire, Hatfield, United Kingdom a1111111111 *
[email protected] Abstract OPEN ACCESS Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibi- Citation: Passmore IJ, Letertre MPM, Preston MD, otic-associated diarrhoea. Disruption of the commensal microbiota, such as through treat- Bianconi I, Harrison MA, Nasher F, et al. (2018) ment with broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile Para-cresol production by Clostridium difficile and subsequent disease. Furthermore, failure of the gut microbiota to recover colonisation affects microbial diversity and membrane integrity of Gram-negative bacteria. PLoS Pathog 14(9): resistance can result in recurrence of infection. An unusual characteristic of C. difficile e1007191. https://doi.org/10.1371/journal. among gut bacteria is its ability to produce the bacteriostatic compound para-cresol (p-cre- ppat.1007191 sol) through fermentation of tyrosine.