In:
PLOS Biology, Public Library of Science (PLoS), Vol. 21, No. 8 ( 2023-8-31), p. e3002253-
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3002253
DOI:
10.1371/journal.pbio.3002253.g001
DOI:
10.1371/journal.pbio.3002253.g002
DOI:
10.1371/journal.pbio.3002253.g003
DOI:
10.1371/journal.pbio.3002253.g004
DOI:
10.1371/journal.pbio.3002253.g005
DOI:
10.1371/journal.pbio.3002253.g006
DOI:
10.1371/journal.pbio.3002253.g007
DOI:
10.1371/journal.pbio.3002253.t001
DOI:
10.1371/journal.pbio.3002253.t002
DOI:
10.1371/journal.pbio.3002253.s001
DOI:
10.1371/journal.pbio.3002253.s002
DOI:
10.1371/journal.pbio.3002253.s003
DOI:
10.1371/journal.pbio.3002253.s004
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10.1371/journal.pbio.3002253.s005
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10.1371/journal.pbio.3002253.s006
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10.1371/journal.pbio.3002253.s007
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10.1371/journal.pbio.3002253.s008
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10.1371/journal.pbio.3002253.s009
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10.1371/journal.pbio.3002253.s010
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10.1371/journal.pbio.3002253.s011
DOI:
10.1371/journal.pbio.3002253.s012
DOI:
10.1371/journal.pbio.3002253.s013
DOI:
10.1371/journal.pbio.3002253.s014
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10.1371/journal.pbio.3002253.s015
DOI:
10.1371/journal.pbio.3002253.s016
DOI:
10.1371/journal.pbio.3002253.s017
DOI:
10.1371/journal.pbio.3002253.s018
DOI:
10.1371/journal.pbio.3002253.s019
DOI:
10.1371/journal.pbio.3002253.s020
DOI:
10.1371/journal.pbio.3002253.s021
DOI:
10.1371/journal.pbio.3002253.s022
DOI:
10.1371/journal.pbio.3002253.s023
DOI:
10.1371/journal.pbio.3002253.s024
DOI:
10.1371/journal.pbio.3002253.s025
DOI:
10.1371/journal.pbio.3002253.s026
DOI:
10.1371/journal.pbio.3002253.s027
DOI:
10.1371/journal.pbio.3002253.s028
DOI:
10.1371/journal.pbio.3002253.s029
DOI:
10.1371/journal.pbio.3002253.s030
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2023
ZDB Id:
2126773-X
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