Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus
A central question to biology is how pathogenic bacteria initiate acute or chronic infections. Here we describe a genetic program for cell-fate decision in the opportunistic human pathogen Staphylococcus aureus, which generates the phenotypic bifurcation of the cells into two genetically identical b...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2017-09-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/28023 |
| _version_ | 1811200324311973888 |
|---|---|
| author | Juan-Carlos García-Betancur Angel Goñi-Moreno Thomas Horger Melanie Schott Malvika Sharan Julian Eikmeier Barbara Wohlmuth Alma Zernecke Knut Ohlsen Christina Kuttler Daniel Lopez |
| author_facet | Juan-Carlos García-Betancur Angel Goñi-Moreno Thomas Horger Melanie Schott Malvika Sharan Julian Eikmeier Barbara Wohlmuth Alma Zernecke Knut Ohlsen Christina Kuttler Daniel Lopez |
| author_sort | Juan-Carlos García-Betancur |
| collection | DOAJ |
| description | A central question to biology is how pathogenic bacteria initiate acute or chronic infections. Here we describe a genetic program for cell-fate decision in the opportunistic human pathogen Staphylococcus aureus, which generates the phenotypic bifurcation of the cells into two genetically identical but different cell types during the course of an infection. Whereas one cell type promotes the formation of biofilms that contribute to chronic infections, the second type is planktonic and produces the toxins that contribute to acute bacteremia. We identified a bimodal switch in the agr quorum sensing system that antagonistically regulates the differentiation of these two physiologically distinct cell types. We found that extracellular signals affect the behavior of the agr bimodal switch and modify the size of the specialized subpopulations in specific colonization niches. For instance, magnesium-enriched colonization niches causes magnesium binding to S. aureusteichoic acids and increases bacterial cell wall rigidity. This signal triggers a genetic program that ultimately downregulates the agr bimodal switch. Colonization niches with different magnesium concentrations influence the bimodal system activity, which defines a distinct ratio between these subpopulations; this in turn leads to distinct infection outcomes in vitro and in an in vivo murine infection model. Cell differentiation generates physiological heterogeneity in clonal bacterial infections and helps to determine the distinct infection types. |
| first_indexed | 2024-04-12T02:01:44Z |
| format | Article |
| id | doaj.art-da421871f1184b77b1f8be354aa35666 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:01:44Z |
| publishDate | 2017-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-da421871f1184b77b1f8be354aa356662022-12-22T03:52:39ZengeLife Sciences Publications LtdeLife2050-084X2017-09-01610.7554/eLife.28023Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureusJuan-Carlos García-Betancur0https://orcid.org/0000-0003-3371-3384Angel Goñi-Moreno1Thomas Horger2Melanie Schott3Malvika Sharan4Julian Eikmeier5https://orcid.org/0000-0002-1576-1174Barbara Wohlmuth6Alma Zernecke7Knut Ohlsen8Christina Kuttler9Daniel Lopez10https://orcid.org/0000-0002-8627-3813Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany; Research Center for Infectious Diseases, University of Würzburg, Würzburg, GermanySchool of Computing Science, Newcastle University, Newcastle, United KingdomDepartment of Mathematics, Technical University of Munich, Garching, GermanyInstitute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg, Würzburg, GermanyInstitute for Molecular Infection Biology, University of Würzburg, Würzburg, GermanyInstitute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany; Research Center for Infectious Diseases, University of Würzburg, Würzburg, GermanyDepartment of Mathematics, Technical University of Munich, Garching, GermanyInstitute of Clinical Biochemistry and Pathobiochemistry, University Hospital Würzburg, Würzburg, GermanyInstitute for Molecular Infection Biology, University of Würzburg, Würzburg, GermanyDepartment of Mathematics, Technical University of Munich, Garching, GermanyInstitute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany; Research Center for Infectious Diseases, University of Würzburg, Würzburg, Germany; National Center for Biotechnology, Madrid, SpainA central question to biology is how pathogenic bacteria initiate acute or chronic infections. Here we describe a genetic program for cell-fate decision in the opportunistic human pathogen Staphylococcus aureus, which generates the phenotypic bifurcation of the cells into two genetically identical but different cell types during the course of an infection. Whereas one cell type promotes the formation of biofilms that contribute to chronic infections, the second type is planktonic and produces the toxins that contribute to acute bacteremia. We identified a bimodal switch in the agr quorum sensing system that antagonistically regulates the differentiation of these two physiologically distinct cell types. We found that extracellular signals affect the behavior of the agr bimodal switch and modify the size of the specialized subpopulations in specific colonization niches. For instance, magnesium-enriched colonization niches causes magnesium binding to S. aureusteichoic acids and increases bacterial cell wall rigidity. This signal triggers a genetic program that ultimately downregulates the agr bimodal switch. Colonization niches with different magnesium concentrations influence the bimodal system activity, which defines a distinct ratio between these subpopulations; this in turn leads to distinct infection outcomes in vitro and in an in vivo murine infection model. Cell differentiation generates physiological heterogeneity in clonal bacterial infections and helps to determine the distinct infection types.https://elifesciences.org/articles/28023Staphylococcus aureuscell differentiationopportunistic infection |
| spellingShingle | Juan-Carlos García-Betancur Angel Goñi-Moreno Thomas Horger Melanie Schott Malvika Sharan Julian Eikmeier Barbara Wohlmuth Alma Zernecke Knut Ohlsen Christina Kuttler Daniel Lopez Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus eLife Staphylococcus aureus cell differentiation opportunistic infection |
| title | Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus |
| title_full | Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus |
| title_fullStr | Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus |
| title_full_unstemmed | Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus |
| title_short | Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus |
| title_sort | cell differentiation defines acute and chronic infection cell types in staphylococcus aureus |
| topic | Staphylococcus aureus cell differentiation opportunistic infection |
| url | https://elifesciences.org/articles/28023 |
| work_keys_str_mv | AT juancarlosgarciabetancur celldifferentiationdefinesacuteandchronicinfectioncelltypesinstaphylococcusaureus AT angelgonimoreno celldifferentiationdefinesacuteandchronicinfectioncelltypesinstaphylococcusaureus AT thomashorger celldifferentiationdefinesacuteandchronicinfectioncelltypesinstaphylococcusaureus AT melanieschott celldifferentiationdefinesacuteandchronicinfectioncelltypesinstaphylococcusaureus AT malvikasharan celldifferentiationdefinesacuteandchronicinfectioncelltypesinstaphylococcusaureus AT julianeikmeier celldifferentiationdefinesacuteandchronicinfectioncelltypesinstaphylococcusaureus AT barbarawohlmuth celldifferentiationdefinesacuteandchronicinfectioncelltypesinstaphylococcusaureus AT almazernecke celldifferentiationdefinesacuteandchronicinfectioncelltypesinstaphylococcusaureus AT knutohlsen celldifferentiationdefinesacuteandchronicinfectioncelltypesinstaphylococcusaureus AT christinakuttler celldifferentiationdefinesacuteandchronicinfectioncelltypesinstaphylococcusaureus AT daniellopez celldifferentiationdefinesacuteandchronicinfectioncelltypesinstaphylococcusaureus |