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Impact of horizontal gene transfer on emergence and stability of cooperative virulence in Salmonella Typhimurium

Erik Bakkeren, Ersin Gül, Jana S. Huisman, Yves Steiger, Andrea Rocker, Wolf-Dietrich Hardt () and Médéric Diard ()
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Erik Bakkeren: Institute of Microbiology, Department of Biology, ETH Zurich
Ersin Gül: Institute of Microbiology, Department of Biology, ETH Zurich
Jana S. Huisman: Institute of Integrative Biology, Department of Environmental Systems Science, ETH Zurich
Yves Steiger: Institute of Microbiology, Department of Biology, ETH Zurich
Andrea Rocker: Biozentrum, University of Basel
Wolf-Dietrich Hardt: Institute of Microbiology, Department of Biology, ETH Zurich
Médéric Diard: Biozentrum, University of Basel

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Intestinal inflammation fuels the transmission of Salmonella Typhimurium (S.Tm). However, a substantial fitness cost is associated with virulence expression. Mutations inactivating transcriptional virulence regulators generate attenuated variants profiting from inflammation without enduring virulence cost. Such variants interfere with the transmission of fully virulent clones. Horizontal transfer of functional regulatory genes (HGT) into attenuated variants could nevertheless favor virulence evolution. To address this hypothesis, we cloned hilD, coding for the master regulator of virulence, into a conjugative plasmid that is highly transferrable during intestinal colonization. The resulting mobile hilD allele allows virulence to emerge from avirulent populations, and to be restored in attenuated mutants competing against virulent clones within-host. However, mutations inactivating the mobile hilD allele quickly arise. The stability of virulence mediated by HGT is strongly limited by its cost, which depends on the hilD expression level, and by the timing of transmission. We conclude that robust evolution of costly virulence expression requires additional selective forces such as narrow population bottlenecks during transmission.

Date: 2022
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DOI: 10.1038/s41467-022-29597-7

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