Clostridioides difficile LuxS mediates inter-bacterial interactions within biofilms.pdf (2.8 MB)
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Clostridioides difficile LuxS mediates inter-bacterial interactions within biofilms.

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posted on 31.07.2019, 09:28 by Ross T. Slater, Lucy R. Frost, Sian E. Jossi, Andrew D. Millard, Meera Unnikrishnan
The anaerobic gut pathogen, Clostridioides difficile, forms adherent biofilms that may play an important role in recurrent C. difficile infections. The mechanisms underlying C. difficile community formation and inter-bacterial interactions are nevertheless poorly understood. C. difficile produces AI-2, a quorum sensing molecule that modulates biofilm formation across many bacterial species. We found that a strain defective in LuxS, the enzyme that mediates AI-2 production, is defective in biofilm development in vitro. Transcriptomic analyses of biofilms formed by wild type (WT) and luxS mutant (luxS) strains revealed a downregulation of prophage loci in the luxS mutant biofilms compared to the WT. Detection of phages and eDNA within biofilms may suggest that DNA release by phage-mediated cell lysis contributes to C. difficile biofilm formation. In order to understand if LuxS mediates C. difficile crosstalk with other gut species, C. difficile interactions with a common gut bacterium, Bacteroides fragilis, were studied. We demonstrate that C. difficile growth is significantly reduced when co-cultured with B. fragilis in mixed biofilms. Interestingly, the absence of C. difficile LuxS alleviates the B. fragilis-mediated growth inhibition. Dual species RNA-sequencing analyses from single and mixed biofilms revealed differential modulation of distinct metabolic pathways for C. difficile WT, luxS and B. fragilis upon co-culture, indicating that AI-2 may be involved in induction of selective metabolic responses in B. fragilis. Overall, our data suggest that C. difficile LuxS/AI-2 utilises different mechanisms to mediate formation of single and mixed species communities.


We thank Gianfranco Donelli, and Claudia Vuotto, Microbial Biofilm Laboratory, IRCCS Fondazione Santa Lucia, Italy for providing the Bacteroides fragilis isolate and Prof Paul Williams, University of Nottingham for providing the Vibrio harveyi strain BB170. This was in part supported by a Seed grant from the Wellcome Warwick Quantitative Biomedicine Programme (Institutional Strategic Support Fund: 105627/Z/14/Z). We thank the Biotechnology and Biological Sciences Research Council (BBSRC) funded Midland Integrative Biosciences Training Partnership (MIBTP) studentships to LF and SR.



Scientific Reports, 2019, volume 9, Article number: 9903

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/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Infection, Immunity and Inflammation


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