Unsaturated Long Chain Free Fatty Acids Are Input Signals of the Salmonella enterica PhoP/PhoQ Regulatory System

Viarengo, Gastón; Sciara, Mariela; Salazar, Mario O.; Kieffer, Pablo M.; Furlán, Ricardo L. E.; Véscovi, Eleonora Garcı́a

doi:10.1074/jbc.m113.472829

Cited by 38 publications

(46 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The PhoQ protein responds to a mildly acidic pH (13, 17), low Mg 2+ (18), certain antimicrobial peptides (19), unsaturated long chain fatty acids (64), acetate concentrations (65), and the redox state in the periplasmic space (66). Which of these signals activates PhoQ during Salmonella infection of its mammalian hosts?…”

Section: Discussionmentioning

confidence: 99%

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

Choi

Groisman

2017

Sci. Signal.

View full text Add to dashboard Cite

The ability to respond to changes in pH is critical for all organisms. In Salmonella enterica, 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 has been 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 S. 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. Thus, 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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Choi

Groisman

2017

Sci. Signal.

View full text Add to dashboard Cite

show abstract

“…Minimum inhibitory concentration (MIC) assays were carried out for palmitoleic acid, linoleic acid and linolenic acid in order to exclude bactericidal activity and to define subinhibitory concentrations for subsequent experiments. Inhibition on the expression was also obtained when the action of linoleic and linolenic fatty acids were assayed using well‐known PhoP‐regulated genes other than virK , indicating that the effect was global on the PhoP–PhoQ controlled regulon (Viarengo et al ., ).…”

Section: Resultsmentioning

confidence: 99%

A Thin‐layer Chromatography Autographic Method for the Detection of Inhibitors of the Salmonella PhoP–PhoQ Regulatory System

Salazar

Viarengo

Sciara

et al. 2013

Phytochemical Analysis

Self Cite

View full text Add to dashboard Cite

show abstract

“…The apparent enrichment of pH-responsive histidines outside of the canonical ligand-binding region (PDC-1) of this family of sensors (Cheung and Hendrickson, 2010;Zhang and Hendrickson, 2010) suggests that SsrA has evolved to integrate pH information in conjunction with another putative ligand(s). The PhoQ sensor in Salmonella has also evolved unique modifications in the membraneproximal PDC domain to integrate multiple inputs such as antimicrobial peptides, pH and fatty acids (Bader et al, 2003;Prost et al, 2007;Viarengo et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Multiple histidines in the periplasmic domain of the Salmonella enterica sensor kinase SsrA enhance signaling in response to extracellular acidification

Mulder

McPhee

Reid-Yu

et al. 2015

Molecular Microbiology

View full text Add to dashboard Cite

SummaryThe two-component regulatory system SsrA-SsrB in Salmonella enterica controls expression of a virulence gene program required for intracellular survival in host cells. SsrA signaling is induced within the acidic host vacuole in which the bacteria reside; however, the mechanism by which SsrA senses this intracellular environment is unknown. Here, we show that the periplasmic sensor domain of SsrA is enriched in histidine residues that increase SsrA signaling below external pH of 6. While no single histidine accounted for the full acid-responsiveness of SsrA, we localized the acid-responsiveness principally to five histidines in the C-terminal end of the periplasmic sensor domain, with input from additional histidines in the N-terminal end of the senor. A sensor mutant lacking critical pH-responsive histidines was defective for acid-promoted activity, yet retained basal activity similar to wild type at neutral pH, indicating that the role of these histidines is to enhance signaling in response to acidification. In support of this, a pH-blind mutant was insensitive to the vacuole acidification blocking activity of bafilomycin, and was attenuated for competitive fitness during infection of mice. Our data demonstrate that SsrA contains a histidine-rich periplasmic sensor that enhances signaling in response to the innate host defense of vacuolar acidification.

show abstract

Unsaturated Long Chain Free Fatty Acids Are Input Signals of the Salmonella enterica PhoP/PhoQ Regulatory System

Cited by 38 publications

References 66 publications

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

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

A Thin‐layer Chromatography Autographic Method for the Detection of Inhibitors of the Salmonella PhoP–PhoQ Regulatory System

Multiple histidines in the periplasmic domain of the Salmonella enterica sensor kinase SsrA enhance signaling in response to extracellular acidification

Contact Info

Product

Resources

About