The LysR-type transcriptional regulator Hrg counteracts phagocyte oxidative burst and imparts survival advantage to Salmonella enterica serovar Typhimurium

Abstract

LysR-type transcriptional regulators (LTTRs) are one of the key players that help bacteria adapt to different environments. We have designated STM0952, a putative LTTR in Salmonella enterica serovar Typhimurium (S. Typhimurium), as hydrogen peroxide resistance gene (hrg). A hrg knockout mutant of S. Typhimurium was sensitive to oxidative products of the respiratory burst, specifically to H(2)O(2). The hrg mutant is profoundly attenuated in a murine model of infection and showed decreased intracellular proliferation in macrophages. It also induced increased amounts of reactive oxygen species and co-localization with gp91phox in the macrophage cell line, when compared to the wild-type. A strain overexpressing the hrg gene showed a survival advantage over the wild-type Salmonella under H(2)O(2)-induced stress. Microarray analysis suggested the presence of an Hrg regulon, which is required for resistance to the toxic oxidative products of the reticuloendothelial system.