CdsH Contributes to the Replication of Typhimurium inside Epithelial Cells in a Cysteine-Supplemented Medium.

Typhimurium is a facultative, intracellular pathogen whose products range from self-limited gastroenteritis to systemic diseases. Food ingestion increases biomolecules' concentration in the intestinal lumen, including amino acids such as cysteine, which is toxic in a concentration-dependent manner. When cysteine's intracellular concentration reaches toxic levels, . Typhimurium expresses a cysteine-inducible enzyme (CdsH), which converts cysteine into pyruvate, sulfide, and ammonia. Despite this evidence, the biological context of 's role is not completely clear, especially in the infective cycle. Since inside epithelial cells both and its positive regulator, , are overexpressed, we hypothesized a possible role of in the intestinal phase of the infection. To test this hypothesis, we used an in vitro model of HT-29 cell infection, adding extra cysteine to the culture medium during the infective process. We observed that, at 6 h post-invasion, the wild type Typhimurium proliferated 30% more than the Δ strain in the presence of extra cysteine. This result shows that contributes to the bacterial replication in the intracellular environment in increased concentrations of extracellular cysteine, strongly suggesting that participates by increasing the bacterial fitness in the intestinal phase of the Typhimurium infection.