Context-dependent change in the fitness effect of (in)organic phosphate antiporter glpT during Salmonella Typhimurium infection

TL;DR

The study shows how Salmonella mutants lacking glpT have different survival advantages in the gut versus inside immune cells.

Contribution

The paper reveals antagonistic pleiotropy of glpT-deficiency in Salmonella during infection stages.

Findings

glpT-deficient mutants thrive in the gut lumen due to reduced phosphate import.

These mutants are counter-selected by macrophages, indicating niche-specific adaptation.

The study highlights spatial and temporal fitness heterogeneity in Salmonella infection.

Abstract

Salmonella enterica is a frequent cause of foodborne diseases, which is attributed to its adaptability. Even within a single host, expressing a gene can be beneficial in certain infection stages but neutral or even detrimental in others as previously shown for flagellins. Mutants deficient for the conserved glycerol-3-phosphate and phosphate antiporter glpT have been shown to be positively selected in nature, clinical, and laboratory settings. This suggests that different selective pressures select for the presence or absence of GlpT in a context dependent fashion, a phenomenon known as antagonistic pleiotropy. Using mutant libraries and reporters, we investigated the fitness of glpT-deficient mutants during murine orogastric infection. While glpT-deficient mutants thrive during initial growth in the gut lumen, where GlpT’s capacity to import phosphate is disadvantageous, they are counter-selected by macrophages. The dichotomy showcases the need to study the spatial and temporal heterogeneity of enteric pathogens’ fitness across distinct lifestyles and niches. Insights into the differential adaptation during infection may reveal opportunities for therapeutic interventions.

Here, Santamaria de Souza et al. explore the context-dependent fitness effects of glpT-deficiency in Salmonella enterica, showing mutants thrive in the gut lumen but are counter-selected by macrophages, highlighting antagonistic pleiotropy and niche-dependent adaptation.

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