DsbA and MgrB Regulate steA Expression through the Two-Component System PhoQ/PhoP in Salmonella enterica

SteA is a protein that can be translocated into host cells through the two virulence-related type III secretion systems that are present in Salmonella enterica. We used the T-POP system to carry out general screens for loci that exhibited activation or repression of a steA::lacZ fusion. These screens identified the histidine kinase PhoQ and the response regulator PhoP as positive regulators of steA. Transcription of this gene is sigma 70 dependent, and the promoter of steA contains a PhoP-binding site that mediates direct regulation by PhoP. Our screens also detected MgrB (also known as YobG) as a negative regulator of the expression of steA. Disruption of the gene encoding the periplasmic disulfide oxidoreductase DsbA or addition of the reducing agent dithiothreitol increases transcription of steA. The effects of MgrB and DsbA on steA are mediated by PhoP. These results suggest that the cellular redox status is a factor contributing to regulation of steA and, probably, other virulence genes regulated by the PhoQ/PhoP two-component system.