Clostridioides difficile LuxS mediates inter-bacterial interactions within biofilms
Abstract 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 pr...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2019-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-019-46143-6 |
| _version_ | 1818346666162388992 |
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| author | Ross T. Slater Lucy R. Frost Sian E. Jossi Andrew D. Millard Meera Unnikrishnan |
| author_facet | Ross T. Slater Lucy R. Frost Sian E. Jossi Andrew D. Millard Meera Unnikrishnan |
| author_sort | Ross T. Slater |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-13T17:21:53Z |
| format | Article |
| id | doaj.art-f3b0901153dc407aa7e0aef5a4b78572 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T17:21:53Z |
| publishDate | 2019-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f3b0901153dc407aa7e0aef5a4b785722022-12-21T23:37:18ZengNature PortfolioScientific Reports2045-23222019-07-019111510.1038/s41598-019-46143-6Clostridioides difficile LuxS mediates inter-bacterial interactions within biofilmsRoss T. Slater0Lucy R. Frost1Sian E. Jossi2Andrew D. Millard3Meera Unnikrishnan4University of WarwickUniversity of WarwickUniversity of WarwickUniversity of LeicesterUniversity of WarwickAbstract 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.https://doi.org/10.1038/s41598-019-46143-6 |
| spellingShingle | Ross T. Slater Lucy R. Frost Sian E. Jossi Andrew D. Millard Meera Unnikrishnan Clostridioides difficile LuxS mediates inter-bacterial interactions within biofilms Scientific Reports |
| title | Clostridioides difficile LuxS mediates inter-bacterial interactions within biofilms |
| title_full | Clostridioides difficile LuxS mediates inter-bacterial interactions within biofilms |
| title_fullStr | Clostridioides difficile LuxS mediates inter-bacterial interactions within biofilms |
| title_full_unstemmed | Clostridioides difficile LuxS mediates inter-bacterial interactions within biofilms |
| title_short | Clostridioides difficile LuxS mediates inter-bacterial interactions within biofilms |
| title_sort | clostridioides difficile luxs mediates inter bacterial interactions within biofilms |
| url | https://doi.org/10.1038/s41598-019-46143-6 |
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