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Updated: Feb 23, 2026

High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages
Published on: August 11, 2014
Basic Processes in Salmonella-Host Interactions: Within-Host Evolution and the Transmission of the Virulent Genotype
Médéric Diard1, Wolf-Dietrich Hardt1
1Institute of Microbiology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Abstract:
Transmission and virulence are central aspects of pathogen evolution. However, in many cases their interconnection has proven difficult to assess by experimentation. Here we discuss recent advances from a mouse model for Salmonella diarrhea. Mouse models mimic the enhanced susceptibility of antibiotic-treated individuals to nontyphoidal salmonellosis. In streptomycin-pretreated mice, Salmonella enterica subspecies 1 serovar Typhimurium efficiently colonizes the gut lumen and elicits pronounced enteropathy. In the host's gut, S. Typhimurium forms two subpopulations that cooperate to elicit disease and optimize transmission. The disease-causing subpopulation expresses a set of dedicated virulence factors (the type 3 secretion system 1 [TTSS-1]) that drive gut tissue invasion. The virulence factor expression is "costly" by retarding the growth rate and exposing the pathogen to innate immune defenses within the gut tissue. These costs are compensated by the gut inflammation (a "public good") that is induced by the invading subpopulation. The inflamed gut lumen fuels S. Typhimurium growth, in particular that of the TTSS-1 "off" subpopulation. The latter grows up to very high densities and promotes transmission. Thus, both phenotypes cooperate to elicit disease and ensure transmission. This system has provided an experimental framework for studying within-host evolution of pathogen virulence, how cooperative virulence is stabilized, and how environmental changes (e.g., antibiotic therapy) affect the transmission of the virulent genotype.
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