The Role of the Host in Driving Phenotypic Heterogeneity in Salmonella

The complex infection environment within hosts exerts unique stresses across tissues and cell types, selecting for phenotypic heterogeneity in bacterial populations. Pathogens maintain variability during infection as a strategy to cope with fluctuating host immune conditions, leading to diversification of virulence phenotypes. Recent improvements in single-cell analyses have revealed that distinct bacterial subpopulations contribute unique colonization and growth strategies across infection sites. We discuss several examples of host-driven phenotypic heterogeneity in Salmonella populations throughout the course of infection, highlighting how variation in gene expression, growth rate, immune evasion, and metabolic activity contribute to overall bacterial success at the population level. We additionally focus our discussion on the implications of diversity within bacterial communities for antimicrobial efficacy.