Phase variation of a signal transduction system controls Clostridioides difficile colony morphology, motility, and virulence.
Recent work has revealed that Clostridioides difficile, a major cause of nosocomial diarrheal disease, exhibits phenotypic heterogeneity within a clonal population as a result of phase variation. Many C. difficile strains representing multiple ribotypes develop two colony morphotypes, termed rough a...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-10-01
|
| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3000379 |
| _version_ | 1811330261825093632 |
|---|---|
| author | Elizabeth M Garrett Ognjen Sekulovic Daniela Wetzel Joshua B Jones Adrianne N Edwards Germán Vargas-Cuebas Shonna M McBride Rita Tamayo |
| author_facet | Elizabeth M Garrett Ognjen Sekulovic Daniela Wetzel Joshua B Jones Adrianne N Edwards Germán Vargas-Cuebas Shonna M McBride Rita Tamayo |
| author_sort | Elizabeth M Garrett |
| collection | DOAJ |
| description | Recent work has revealed that Clostridioides difficile, a major cause of nosocomial diarrheal disease, exhibits phenotypic heterogeneity within a clonal population as a result of phase variation. Many C. difficile strains representing multiple ribotypes develop two colony morphotypes, termed rough and smooth, but the biological implications of this phenomenon have not been explored. Here, we examine the molecular basis and physiological relevance of the distinct colony morphotypes produced by this bacterium. We show that C. difficile reversibly differentiates into rough and smooth colony morphologies and that bacteria derived from the isolates display discrete motility behaviors. We identified an atypical phase-variable signal transduction system consisting of a histidine kinase and two response regulators, named herein colony morphology regulators RST (CmrRST), which mediates the switch in colony morphology and motility behaviors. The CmrRST-regulated surface motility is independent of flagella and type IV pili, suggesting a novel mechanism of cell migration in C. difficile. Microscopic analysis of cell and colony structure indicates that CmrRST promotes the formation of elongated bacteria arranged in bundled chains, which may contribute to bacterial migration on surfaces. In a hamster model of acute C. difficile disease, the CmrRST system is required for disease development. Furthermore, we provide evidence that CmrRST phase varies during infection, suggesting that the intestinal environment impacts the proportion of CmrRST-expressing C. difficile. Our findings indicate that C. difficile employs phase variation of the CmrRST signal transduction system to generate phenotypic heterogeneity during infection, with concomitant effects on bacterial physiology and pathogenesis. |
| first_indexed | 2024-04-13T15:59:24Z |
| format | Article |
| id | doaj.art-599f095f0f464566b9a4dffd604ce2d9 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-04-13T15:59:24Z |
| publishDate | 2019-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-599f095f0f464566b9a4dffd604ce2d92022-12-22T02:40:35ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852019-10-011710e300037910.1371/journal.pbio.3000379Phase variation of a signal transduction system controls Clostridioides difficile colony morphology, motility, and virulence.Elizabeth M GarrettOgnjen SekulovicDaniela WetzelJoshua B JonesAdrianne N EdwardsGermán Vargas-CuebasShonna M McBrideRita TamayoRecent work has revealed that Clostridioides difficile, a major cause of nosocomial diarrheal disease, exhibits phenotypic heterogeneity within a clonal population as a result of phase variation. Many C. difficile strains representing multiple ribotypes develop two colony morphotypes, termed rough and smooth, but the biological implications of this phenomenon have not been explored. Here, we examine the molecular basis and physiological relevance of the distinct colony morphotypes produced by this bacterium. We show that C. difficile reversibly differentiates into rough and smooth colony morphologies and that bacteria derived from the isolates display discrete motility behaviors. We identified an atypical phase-variable signal transduction system consisting of a histidine kinase and two response regulators, named herein colony morphology regulators RST (CmrRST), which mediates the switch in colony morphology and motility behaviors. The CmrRST-regulated surface motility is independent of flagella and type IV pili, suggesting a novel mechanism of cell migration in C. difficile. Microscopic analysis of cell and colony structure indicates that CmrRST promotes the formation of elongated bacteria arranged in bundled chains, which may contribute to bacterial migration on surfaces. In a hamster model of acute C. difficile disease, the CmrRST system is required for disease development. Furthermore, we provide evidence that CmrRST phase varies during infection, suggesting that the intestinal environment impacts the proportion of CmrRST-expressing C. difficile. Our findings indicate that C. difficile employs phase variation of the CmrRST signal transduction system to generate phenotypic heterogeneity during infection, with concomitant effects on bacterial physiology and pathogenesis.https://doi.org/10.1371/journal.pbio.3000379 |
| spellingShingle | Elizabeth M Garrett Ognjen Sekulovic Daniela Wetzel Joshua B Jones Adrianne N Edwards Germán Vargas-Cuebas Shonna M McBride Rita Tamayo Phase variation of a signal transduction system controls Clostridioides difficile colony morphology, motility, and virulence. PLoS Biology |
| title | Phase variation of a signal transduction system controls Clostridioides difficile colony morphology, motility, and virulence. |
| title_full | Phase variation of a signal transduction system controls Clostridioides difficile colony morphology, motility, and virulence. |
| title_fullStr | Phase variation of a signal transduction system controls Clostridioides difficile colony morphology, motility, and virulence. |
| title_full_unstemmed | Phase variation of a signal transduction system controls Clostridioides difficile colony morphology, motility, and virulence. |
| title_short | Phase variation of a signal transduction system controls Clostridioides difficile colony morphology, motility, and virulence. |
| title_sort | phase variation of a signal transduction system controls clostridioides difficile colony morphology motility and virulence |
| url | https://doi.org/10.1371/journal.pbio.3000379 |
| work_keys_str_mv | AT elizabethmgarrett phasevariationofasignaltransductionsystemcontrolsclostridioidesdifficilecolonymorphologymotilityandvirulence AT ognjensekulovic phasevariationofasignaltransductionsystemcontrolsclostridioidesdifficilecolonymorphologymotilityandvirulence AT danielawetzel phasevariationofasignaltransductionsystemcontrolsclostridioidesdifficilecolonymorphologymotilityandvirulence AT joshuabjones phasevariationofasignaltransductionsystemcontrolsclostridioidesdifficilecolonymorphologymotilityandvirulence AT adriannenedwards phasevariationofasignaltransductionsystemcontrolsclostridioidesdifficilecolonymorphologymotilityandvirulence AT germanvargascuebas phasevariationofasignaltransductionsystemcontrolsclostridioidesdifficilecolonymorphologymotilityandvirulence AT shonnammcbride phasevariationofasignaltransductionsystemcontrolsclostridioidesdifficilecolonymorphologymotilityandvirulence AT ritatamayo phasevariationofasignaltransductionsystemcontrolsclostridioidesdifficilecolonymorphologymotilityandvirulence |