Context-dependent change in the fitness effect of (in)organic phosphate antiporter glpT during Salmonella Typhimurium infection
Abstract Salmonella enterica is a frequent cause of foodborne diseases, which is attributed to its adaptability. Even within a single host, expressing a gene can be beneficial in certain infection stages but neutral or even detrimental in others as previously shown for flagellins. Mutants deficient...
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56851-5 |
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| author | Noemi Santamaria de Souza Yassine Cherrak Thea Bill Andersen Michel Vetsch Manja Barthel Sanne Kroon Erik Bakkeren Christopher Schubert Philipp Christen Patrick Kiefer Julia A. Vorholt Bidong D. Nguyen Wolf-Dietrich Hardt |
| author_facet | Noemi Santamaria de Souza Yassine Cherrak Thea Bill Andersen Michel Vetsch Manja Barthel Sanne Kroon Erik Bakkeren Christopher Schubert Philipp Christen Patrick Kiefer Julia A. Vorholt Bidong D. Nguyen Wolf-Dietrich Hardt |
| author_sort | Noemi Santamaria de Souza |
| collection | DOAJ |
| description | Abstract Salmonella enterica is a frequent cause of foodborne diseases, which is attributed to its adaptability. Even within a single host, expressing a gene can be beneficial in certain infection stages but neutral or even detrimental in others as previously shown for flagellins. Mutants deficient for the conserved glycerol-3-phosphate and phosphate antiporter glpT have been shown to be positively selected in nature, clinical, and laboratory settings. This suggests that different selective pressures select for the presence or absence of GlpT in a context dependent fashion, a phenomenon known as antagonistic pleiotropy. Using mutant libraries and reporters, we investigated the fitness of glpT-deficient mutants during murine orogastric infection. While glpT-deficient mutants thrive during initial growth in the gut lumen, where GlpT’s capacity to import phosphate is disadvantageous, they are counter-selected by macrophages. The dichotomy showcases the need to study the spatial and temporal heterogeneity of enteric pathogens’ fitness across distinct lifestyles and niches. Insights into the differential adaptation during infection may reveal opportunities for therapeutic interventions. |
| format | Article |
| id | doaj-art-682a2971f89c44cdbf315c11995cbda2 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-682a2971f89c44cdbf315c11995cbda22025-08-20T02:59:28ZengNature PortfolioNature Communications2041-17232025-02-0116111910.1038/s41467-025-56851-5Context-dependent change in the fitness effect of (in)organic phosphate antiporter glpT during Salmonella Typhimurium infectionNoemi Santamaria de Souza0Yassine Cherrak1Thea Bill Andersen2Michel Vetsch3Manja Barthel4Sanne Kroon5Erik Bakkeren6Christopher Schubert7Philipp Christen8Patrick Kiefer9Julia A. Vorholt10Bidong D. Nguyen11Wolf-Dietrich Hardt12Department of Biology, Institute of Microbiology, ETH ZürichDepartment of Biology, Institute of Microbiology, ETH ZürichDepartment of Biology, Institute of Microbiology, ETH ZürichDepartment of Biology, Institute of Microbiology, ETH ZürichDepartment of Biology, Institute of Microbiology, ETH ZürichDepartment of Biology, Institute of Microbiology, ETH ZürichSir William Dunn School of Pathology, University of OxfordDepartment of Biology, Institute of Microbiology, ETH ZürichDepartment of Biology, Institute of Microbiology, ETH ZürichDepartment of Biology, Institute of Microbiology, ETH ZürichDepartment of Biology, Institute of Microbiology, ETH ZürichDepartment of Biology, Institute of Microbiology, ETH ZürichDepartment of Biology, Institute of Microbiology, ETH ZürichAbstract Salmonella enterica is a frequent cause of foodborne diseases, which is attributed to its adaptability. Even within a single host, expressing a gene can be beneficial in certain infection stages but neutral or even detrimental in others as previously shown for flagellins. Mutants deficient for the conserved glycerol-3-phosphate and phosphate antiporter glpT have been shown to be positively selected in nature, clinical, and laboratory settings. This suggests that different selective pressures select for the presence or absence of GlpT in a context dependent fashion, a phenomenon known as antagonistic pleiotropy. Using mutant libraries and reporters, we investigated the fitness of glpT-deficient mutants during murine orogastric infection. While glpT-deficient mutants thrive during initial growth in the gut lumen, where GlpT’s capacity to import phosphate is disadvantageous, they are counter-selected by macrophages. The dichotomy showcases the need to study the spatial and temporal heterogeneity of enteric pathogens’ fitness across distinct lifestyles and niches. Insights into the differential adaptation during infection may reveal opportunities for therapeutic interventions.https://doi.org/10.1038/s41467-025-56851-5 |
| spellingShingle | Noemi Santamaria de Souza Yassine Cherrak Thea Bill Andersen Michel Vetsch Manja Barthel Sanne Kroon Erik Bakkeren Christopher Schubert Philipp Christen Patrick Kiefer Julia A. Vorholt Bidong D. Nguyen Wolf-Dietrich Hardt Context-dependent change in the fitness effect of (in)organic phosphate antiporter glpT during Salmonella Typhimurium infection Nature Communications |
| title | Context-dependent change in the fitness effect of (in)organic phosphate antiporter glpT during Salmonella Typhimurium infection |
| title_full | Context-dependent change in the fitness effect of (in)organic phosphate antiporter glpT during Salmonella Typhimurium infection |
| title_fullStr | Context-dependent change in the fitness effect of (in)organic phosphate antiporter glpT during Salmonella Typhimurium infection |
| title_full_unstemmed | Context-dependent change in the fitness effect of (in)organic phosphate antiporter glpT during Salmonella Typhimurium infection |
| title_short | Context-dependent change in the fitness effect of (in)organic phosphate antiporter glpT during Salmonella Typhimurium infection |
| title_sort | context dependent change in the fitness effect of in organic phosphate antiporter glpt during salmonella typhimurium infection |
| url | https://doi.org/10.1038/s41467-025-56851-5 |
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