The LysR-type transcriptional regulator STM0030 contributes to Salmonella Typhimurium growth in macrophages and virulence in mice.

Abstract

Salmonella enterica serovar Typhimurium (S. Tm) is a major intracellular pathogen that infects humans and animals, and its survival and growth in macrophages is essential for its pathogenicity. More than 50 putative regulatory proteins are encoded by the S. Tm genome, but the functions of these regulatory proteins in mediating S. Tm pathogenicity are largely unknown. In this study, we investigated the biological function of the STM0030 gene, which encodes a putative LysR-type transcriptional regulator. We found that STM0030 is upregulated 2.8-5.7-fold during S. Tm growth in macrophages. Further, mutating this gene decreased bacterial growth in macrophages and attenuated virulence in mice. RNA-sequencing to investigate the regulatory function of STM0030 in S. Tm revealed that 447 genes were differentially expressed between the mutant and the wild-type strains; 429 of these genes were downregulated, suggesting that STM0030 mainly acts as a transcriptional activator. Moreover, the expression of gluconate, maltose, and hexose-p transport genes, as well as allantoin utilization genes were downregulated in the STM0030 mutant; this might be associated with the observed decrease in intracellular replication and pathogenicity of the mutant. Our findings suggest that STM0030 is a new pathogenicity-associated regulatory protein that broadens our understanding of the virulence regulatory network of S. Tm.