The role of mucins in Clostridioides Difficile Infection
Overview
Clostridioides difficile, is the leading cause of hospital-acquired diarrhoea globally and is often acquired following antibiotic use for the treatment of an unrelated infection. An unintended consequence of antibiotic treatment is that it disrupts the gut microbiota, permitting C. difficile infection (CDI). Treatment of CDI requires antibiotics, which further damages the protective gut microbiota, resulting in severe and repeated incidences of diarrhoea. Alternative treatment options and diagnostic tools for CDI are limited and a greater understanding of disease pathogenesis is required for the development of more targeted treatments. The association of this bacterium with the gut mucosa is critical to a successful infection, yet we do not have a good understanding of the initial infection events. In particular, the role of the mucus layer which lines the gut epithelium remains unclear.
Professor Lyras and Dr Unnikrishnan’s preliminary studies employing dual RNA sequencing using a human gut model reveal that the gut mucins, including MUC13, are induced during infection in vitro. This project will investigate the role of host mucins during CDI. This work will help define the gut-pathogen interface of this clinically important pathogen and provide critical information that will inform the downstream rational design of strategies to diagnose and treat this debilitating infection.
Aims/objectives:
Professor Lyras and Dr Unnikrishnan’s overall goal is to understand the role of surface mucins in CDI. In the proposed study, they will focus on one of the immunomodulatory surface mucins, MUC13, which is induced during infection. Utilising the complementary in vitro and in vivo tools available at Warwick and Monash we will investigate the role of MUC13 in CDI.
Processor Lyras and Dr Unnikrishnan expect these initial experiments to lead to a larger collaborative project and joint grant applications that will extend into an in-depth analysis of the role of other gut mucins in CDI. Specifically, this data will form the basis of a larger joint grant application to the Medical Research Council, UK (£800-900K, Response mode September 2023 deadline) and lead to high-quality and high-impact publication. They will also present the results from this study at international enteric disease conferences (e.g., Clostpath, ICDS). This project will also support the development of an advanced human gut mimic, a useful tool with broader applications for studying anaerobic microbiota-gut interactions, which will open up further new collaborations.
Principle applicants
 Professor, Department of Microbiology - Monash University |  Faculty of Science, Engineering and Medicine - University of Warwick |
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Co-applicants
Dr Melanie Hutton - Monash University
Mr Thomas MacReath - University of Warwick