Research ArticleMicrobiology

Activation of master virulence regulator PhoP in acidic pH requires the Salmonella-specific protein UgtL

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Sci. Signal.  29 Aug 2017:
Vol. 10, Issue 494, eaan6284
DOI: 10.1126/scisignal.aan6284

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A helping hand for acid sensing

Activation of the PhoP/PhoQ two-component system of Salmonella enterica promotes the expression of virulence factors. Stimuli, such as acidic pH, low Mg2+, or antimicrobial peptides, stimulate the sensor kinase PhoQ to undergo autophosphorylation, which enables PhoQ to phosphorylate the response regulator PhoP. Phosphorylated PhoP then binds to and stimulates the transcription of target genes. Choi and Groisman found that the Salmonella-specific protein UgtL enhanced acid-induced activation of the PhoP/PhoQ system but had no effect on the activation of this system by low Mg2+ or antimicrobial peptides. UgtL promoted the phosphorylation of PhoP by enhancing the autophosphorylation of PhoQ, but it had no effects on phosphotransfer from PhoQ to PhoP or dephosphorylation of PhoP by PhoQ. Compared to wild-type Salmonella, ugtL mutants exhibited reduced virulence in mice. Thus, this horizontally acquired factor has become an important determinant of Salmonella virulence.

Abstract

Acidic conditions, such as those inside phagosomes, stimulate the intracellular pathogen Salmonella enterica to activate virulence genes. The sensor PhoQ responds to a mildly acidic pH by phosphorylating, and thereby activating, the virulence regulator PhoP. This PhoP/PhoQ two-component system is conserved in a subset of Gram-negative bacteria. PhoQ is thought to be sufficient to activate PhoP in mildly acidic pH. However, we found that the Salmonella-specific protein UgtL, which was horizontally acquired by Salmonella before the divergence of S. enterica and Salmonella bongori, was also necessary for PhoQ to activate PhoP under mildly acidic pH conditions but not for PhoQ to activate PhoP in response to low Mg2+ or the antimicrobial peptide C18G. UgtL increased the abundance of phosphorylated PhoP by stimulating autophosphorylation of PhoQ, thereby increasing the amount of the phosphodonor for PhoP. Deletion of ugtL attenuated Salmonella virulence and further reduced PhoP activation in a strain bearing a form of PhoQ that is not responsive to acidic pH. These data suggest that when Salmonella experiences mildly acidic pH, PhoP activation requires PhoQ to detect pH and UgtL to amplify the PhoQ response. Our findings reveal how acquisition of a foreign gene can strengthen signal responsiveness in an ancestral regulatory system.

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