Journal
EMBO JOURNAL
Volume 19, Issue 8, Pages 1861-1872Publisher
WILEY
DOI: 10.1093/emboj/19.8.1861
Keywords
magnesium; PhoP-PhoQ; PmrA-PmrB; signal transduction; transcription
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Funding
- NIAID NIH HHS [AI42236, R56 AI042236, R01 AI042236] Funding Source: Medline
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The PmrA-PmrB two-component system of Salmonella enterica controls resistance to the peptide antibiotic polymyxin B and to several antimicrobial proteins from human neutrophils. Transcription of PmrA-activated genes is induced by high iron, but can also be promoted by growth in low magnesium in a process that requires another two-component system, PhoP-PhoQ. Here, we define the genetic basis for the interaction between the PhoP-PhoQ and PmrA-PmrB systems. We have identified pmrD as a PhoP-activated gene that mediates the transcriptional activation of PmrA-regulated genes during growth in low magnesium. When transcription of pmrD is driven from a heterologous promoter, expression of PmrA-activated genes occurs even at repressing magnesium concentrations and becomes independent of the phoP and phoQ genes. The PmrD effect is specific for PmrA-regulated genes and requires functional PmrA and PmrB proteins, A pmrD mutant is sensitive to polymyxin if grown in low magnesium, but resistant if grown in high iron. The PmrD protein controls the activity of the PmrA-PmrB system at a post-transcriptional level.
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