Bacterial infections are multifactorial processes that often involve a complex interaction between the pathogen and resident microbial community. We have developed an in vitro microbioreactor array system to cultivate human microbial communities and explore how they react to invasion by pathogens. Using this system, we have developed a model of Clostridioides difficile infection of a human microbiome that has been disrupted by antibiotics. Through investigating how C. difficile ribotypes compete with one another to cause disease, we found that adaptation of C. difficile to the diet is contributing the evolution of pathogenesis. We expect that many other bacteria, both pathogenic and symbiotic, are also likely undergoing evolution to our diet. By understanding this complex interaction, we aim to identify novel therapeutic microbial communities that can be used to not only treat recurrent C. difficile infection but also used prophylactically to prevent primary infections.
Selected Publications
Midani FS, Danhof HA, Mathew N, Ardis CK, Garey KW, Spinler JK, Britton RA. Emerging Clostridioides difficile ribotypes have divergent metabolic phenotypes. mSystems. 2025 Mar 18;10(3):e0107524. doi: 10.1128/msystems.01075-24. Epub 2025 Feb 27. PMID: 40013784; PMCID: PMC11915817.
Zhu D, Wozniak KJ, Midani F, Wang S, Sun X, Britton RA. Control of Clostridioides difficile virulence and physiology by the flagellin homeostasis checkpoint FliC-FliW-CsrA in the absence of motility. mBio. 2025 Mar 12;16(3):e0380124. doi: 10.1128/mbio.03801-24. Epub 2025 Jan 30. PMID: 39882902; PMCID: PMC11898703.
Midani FS, Collins J, Britton RA. AMiGA: Software for Automated Analysis of Microbial Growth Assays. mSystems. 2021 Aug 31;6(4):e0050821. doi: 10.1128/mSystems.00508-21. Epub 2021 Jul 13. PMID: 34254821; PMCID: PMC8409736.
Auchtung JM, Preisner EC, Collins J, Lerma AI, Britton RA. Identification of Simplified Microbial Communities That Inhibit Clostridioides difficile Infection through Dilution/Extinction. mSphere. 2020 Jul 29;5(4):e00387-20. doi: 10.1128/mSphere.00387-20. PMID: 32727857; PMCID: PMC7392540.
Collins J, Danhof H, Britton RA. The role of trehalose in the global spread of epidemic Clostridium difficile. Gut Microbes. 2019;10(2):204-209. doi: 10.1080/19490976.2018.1491266. Epub 2018 Aug 17. PMID: 30118389; PMCID: PMC6546318.
Collins J, Robinson C, Danhof H, Knetsch CW, van Leeuwen HC, Lawley TD, Auchtung JM, Britton RA. (2018). Dietary trehalose enhances virulence of epidemic Clostridium difficile. Nature. 2018 Jan 18;553 (7688):291-294. PMID: 29310122.
Auchtung JM, Robinson CD, Farrell K, Britton RA. MiniBioReactor Arrays (MBRAs) as a Tool for Studying C. difficile Physiology in the Presence of a Complex Community. Methods Mol Biol. 2016;1476:235-58. doi: 10.1007/978-1-4939-6361-4_18.