The expression of virulence genes increases membrane permeability and sensitivity to envelope stress in Salmonella Typhimurium

Virulence gene expression can represent a substantial fitness cost to pathogenic bacteria. In the model entero-pathogen Salmonella Typhimurium (S.Tm), such cost favors emergence of attenuated variants during infections that harbor mutations in transcriptional activators of virulence genes (e.g., hil...

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Published in:	PLoS biology Vol. 20; no. 4; p. e3001608
Main Authors:	Sobota, Malgorzata, Rodilla Ramirez, Pilar Natalia, Cambré, Alexander, Rocker, Andrea, Mortier, Julien, Gervais, Théo, Haas, Tiphaine, Cornillet, Delphine, Chauvin, Dany, Hug, Isabelle, Julou, Thomas, Aertsen, Abram, Diard, Médéric
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 07-04-2022 Public Library of Science (PLoS)
Subjects:	Animals Bacteria Bacterial Proteins - metabolism Biology and Life Sciences Experiments Gene expression Gene Expression Regulation, Bacterial Genes Genetic aspects Harsh environments Infections Medicine and Health Sciences Membrane permeability Membranes Mice Microscopy Mutation Observations Pathogens Permeability Physical Sciences Population Research and Analysis Methods Salmonella Salmonella Typhimurium Salmonella typhimurium - genetics Salmonella typhimurium - metabolism Sensitivity Short Reports Stress Transcription factors Virulence Virulence (Microbiology) Virulence - genetics Virulence factors Virulence Factors - genetics Virulence Factors - metabolism United States
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Summary:	Virulence gene expression can represent a substantial fitness cost to pathogenic bacteria. In the model entero-pathogen Salmonella Typhimurium (S.Tm), such cost favors emergence of attenuated variants during infections that harbor mutations in transcriptional activators of virulence genes (e.g., hilD and hilC). Therefore, understanding the cost of virulence and how it relates to virulence regulation could allow the identification and modulation of ecological factors to drive the evolution of S.Tm toward attenuation. In this study, investigations of membrane status and stress resistance demonstrate that the wild-type (WT) expression level of virulence factors embedded in the envelope increases membrane permeability and sensitizes S.Tm to membrane stress. This is independent from a previously described growth defect associated with virulence gene expression in S.Tm. Pretreating the bacteria with sublethal stress inhibited virulence expression and increased stress resistance. This trade-off between virulence and stress resistance could explain the repression of virulence expression in response to harsh environments in S.Tm. Moreover, we show that virulence-associated stress sensitivity is a burden during infection in mice, contributing to the inherent instability of S.Tm virulence. As most bacterial pathogens critically rely on deploying virulence factors in their membrane, our findings could have a broad impact toward the development of antivirulence strategies.
Bibliography:	new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors have declared that no competing interests exist.
ISSN:	1545-7885 1544-9173 1545-7885
DOI:	10.1371/journal.pbio.3001608