The microbiota conditions a gut milieu that selects for wild-type Salmonella Typhimurium virulence
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Published:2023-08-31
Issue:8
Volume:21
Page:e3002253
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ISSN:1545-7885
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Container-title:PLOS Biology
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language:en
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Short-container-title:PLoS Biol
Author:
Gül Ersin,
Bakkeren Erik,
Salazar Guillem,
Steiger Yves,
Abi Younes Andrew,
Clerc Melanie,
Christen Philipp,
Fattinger Stefan A.,
Nguyen Bidong D.,
Kiefer Patrick,
Slack Emma,
Ackermann Martin,
Vorholt Julia A.,
Sunagawa Shinichi,
Diard Médéric,
Hardt Wolf-DietrichORCID
Abstract
Salmonella Typhimurium elicits gut inflammation by the costly expression of HilD-controlled virulence factors. This inflammation alleviates colonization resistance (CR) mediated by the microbiota and thereby promotes pathogen blooms. However, the inflamed gut-milieu can also select for hilD mutants, which cannot elicit or maintain inflammation, therefore causing a loss of the pathogen’s virulence. This raises the question of which conditions support the maintenance of virulence in S. Typhimurium. Indeed, it remains unclear why the wild-type hilD allele is dominant among natural isolates. Here, we show that microbiota transfer from uninfected or recovered hosts leads to rapid clearance of hilD mutants that feature attenuated virulence, and thereby contributes to the preservation of the virulent S. Typhimurium genotype. Using mouse models featuring a range of microbiota compositions and antibiotic- or inflammation-inflicted microbiota disruptions, we found that irreversible disruption of the microbiota leads to the accumulation of hilD mutants. In contrast, in models with a transient microbiota disruption, selection for hilD mutants was prevented by the regrowing microbiota community dominated by Lachnospirales and Oscillospirales. Strikingly, even after an irreversible microbiota disruption, microbiota transfer from uninfected donors prevented the rise of hilD mutants. Our results establish that robust S. Typhimurium gut colonization hinges on optimizing its manipulation of the host: A transient and tempered microbiota perturbation is favorable for the pathogen to both flourish in the inflamed gut and also minimize loss of virulence. Moreover, besides conferring CR, the microbiota may have the additional consequence of maintaining costly enteropathogen virulence mechanisms.
Funder
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Gebert Rüf Stiftung
Cree Board of Health and Social Services of James Bay
Geschwister Boehringer Ingelheim Stiftung für Geisteswissenschaften
Botnar Research Centre for Child Health, University of Basel
Publisher
Public Library of Science (PLoS)
Subject
General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Neuroscience
Cited by
1 articles.
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