Microbiota-derived metabolites inhibitSalmonellavirulent subpopulation development by acting on single-cell behaviors

Abstract

Salmonella spp. express Salmonella pathogenicity island 1 (SPI-1) genes to mediate the initial phase of interaction with host cells. Prior studies indicate short-chain fatty acids, microbial metabolites at high concentrations in the gastrointestinal tract, limit SPI-1 gene expression. A number of reports show only a subset of Salmonella cells in a population express these genes, suggesting short-chain fatty acids could decrease SPI-1 population-level expression by acting on per-cell expression and/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 SPI-1 expression. Our results show short-chain fatty acids do not repress SPI-1 expression by individual cells. Rather, these compounds act to selectively slow the growth of SPI-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 SPI-1 cell-type proportions, our findings imply gut microbial metabolites act on cooperation between the two cell-types and ultimately influence the capacity of Salmonella to establish within a host.

Changes in interactions over ecological time scales influence single cell growth dynamics in a metabolically coupled marine microbial community

“…This approach thus allows us to disentangle how metabolic interactions within microbial communities change over time. Previous studies have used similar approaches in order to answer fundamental questions about microbial physiology in clonal populations (25) (26) (27) (28). Here, we use this approach to study the growth dynamics of individual cells in simple microbial communities.…”