Microbiota-derived metabolites inhibit Salmonella virulent subpopulation development by acting on single-cell behaviors
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2021-08-03
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Journal Article
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yes
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Abstract
Salmonella spp. express Salmonella pathogenicity island 1 Type III Secretion System 1 (T3SS-1) genes to mediate the initial phase of interaction with their host. Prior studies indicate short-chain fatty acids, microbial metabolites at high concentrations in the gastrointestinal tract, limit population-level T3SS-1 gene expression. However, only a subset of Salmonella cells in a population express these genes, suggesting short-chain fatty acids could decrease T3SS-1 population-level expression by acting on per-cell expression or the proportion of expressing cells. Here, we combine single-cell, theoretical, and molecular approaches to address the effect of short-chain fatty acids on T3SS-1 expression. Our in vitro results show short-chain fatty acids do not repress T3SS-1 expression by individual cells. Rather, these compounds act to selectively slow the growth of T3SS-1-expressing cells, ultimately decreasing their frequency in the population. Further experiments indicate slowed growth arises from short-chain fatty acid-mediated depletion of the proton motive force. By influencing the T3SS-1 cell-type proportions, our findings imply gut microbial metabolites act on cooperation between the two cell types and ultimately influence Salmonella's capacity to establish within a host.
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published
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118 (31)
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National Academy of Sciences
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Subject
Salmonella; Single cell; Pathogenesis
Organisational unit
03589 - Hardt, Wolf-Dietrich / Hardt, Wolf-Dietrich
03743 - Ackermann, Martin / Ackermann, Martin
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Funding
SEED-23 19-2 - Systems-level view of Salmonella pathogenicity (ETHZ)
169978 - A microscale analysis of the causes and consequences of the spatial arrangement of biological functions in microbial consortia (SNF)
169978 - A microscale analysis of the causes and consequences of the spatial arrangement of biological functions in microbial consortia (SNF)