Two-component regulatory systems can interact to process multiple environmental signals.
The PhoP/PhoQ two-component system of Salmonella typhimurium governs transcription of some 25 loci in response to the extracellular concentration of Mg2+. We have now identified one of these loci as pmrCAB, which codes for a two-component system that mediates resistance to the antibiotic polymyxin B. Transcription of seven of 25 PhoP-activated loci was dependent on a functional PmrA protein, the response regulator of the PmrA/PmrB system. Expression of the PmrA-dependent loci was induced by either Mg2+ limitation or mild acidification, whereas transcription of a PmrA-independent gene was activated by Mg2+ limitation but not acid pH. Induction of PmrA-activated genes by Mg2 limitation required the PhoP and PhoQ proteins. In contrast, the acid-mediated activation of PmrA-regulated genes occurred in strains that were missing either one of these proteins. Transcriptional regulation by a cascade of two-component systems allows pathogenic bacteria to express their virulence determinants in response to a broader spectrum of environmental cues.
Soncini
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Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Groisman
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EA
D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D003470:Culture Media; D015964:Gene Expression Regulation, Bacterial; D006863:Hydrogen-Ion Concentration; D008274:Magnesium / Q000494:pharmacology; D016254:Mutagenesis, Insertional; D009876:Operon; D012486:Salmonella typhimurium / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D001426:Bacterial Proteins; D003470:Culture Media; C079792:PhoQ protein, Bacteria; D014157:Transcription Factors; C081902:pmrA protein, Bacteria; C061064:PhoP protein, Bacteria; D008274:Magnesium