Acidic pH sensing in the bacterial cytoplasm is required for Salmonella virulence.
pH regulates gene expression, biochemical activities and cellular behaviors. A mildly acidic pH activates the master virulence regulatory system PhoP/PhoQ in the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. The sensor PhoQ harbors an extracytoplasmic domain implicated in signal sensing, and a cytoplasmic domain controlling activation of the regulator PhoP. We now report that, surprisingly, a decrease in Salmonella's own cytoplasmic pH induces transcription of PhoP-activated genes even when the extracytoplasmic pH remains neutral. Amino acid substitutions in PhoQ's cytoplasmic domain hindered activation by acidic pH and attenuated virulence in mice, but did not abolish activation by low Mg(2+) or the antimicrobial peptide C18G. Conversely, removal of PhoQ's extracytoplasmic domains prevented the response to the latter PhoQ-activating signals but not to acidic pH. PhoP-dependent genes were minimally induced by acidic pH in the non-pathogenic species Salmonella bongori but were activated by low Mg(2+) and C18G as in pathogenic S. enterica. Our findings indicate that the sensor PhoQ enables S. enterica to respond to both host- and bacterial-derived signals that alter its cytoplasmic pH.
Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT, 06536, USA.
Jeongjoon
J
Choi
Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT, 06536, USA. eduardo.groisman@yale.edu.|Yale Microbial Sciences Institute, West Haven, CT, 06516, USA. eduardo.groisman@yale.edu.
Eduardo A
EA
Groisman
D019943:Amino Acid Substitution; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006863:Hydrogen-Ion Concentration; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D015398:Signal Transduction; D014157:Transcription Factors; D014774:Virulence / Q000502:physiology
D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; C081140:C18G peptide; D010455:Peptides; C079792:PhoQ protein, Bacteria; D014157:Transcription Factors; C061064:PhoP protein, Bacteria; D008274:Magnesium