Acidic pH and divalent cation sensing by PhoQ are dispensable for systemic salmonellae virulence.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26002083.
- Also identified by DOI 10.7554/eLife.06792 and PMC identifier 4473727.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Salmonella PhoQ is a histidine kinase with a periplasmic sensor domain (PD) that promotes virulence by detecting the macrophage phagosome. PhoQ activity is repressed by divalent cations and induced in environments of acidic pH, limited divalent cations, and cationic antimicrobial peptides (CAMP). Previously, it was unclear which signals are sensed by salmonellae to promote PhoQ-mediated virulence. We defined conformational changes produced in the PhoQ PD on exposure to acidic pH that indicate structural flexibility is induced in α-helices 4 and 5, suggesting this region contributes to pH sensing. Therefore, we engineered a disulfide bond between W104C and A128C in the PhoQ PD that restrains conformational flexibility in α-helices 4 and 5. PhoQ(W104C-A128C) is responsive to CAMP, but is inhibited for activation by acidic pH and divalent cation limitation. phoQ(W104C-A128C) Salmonella enterica Typhimurium is virulent in mice, indicating that acidic pH and divalent cation sensing by PhoQ are dispensable for virulence.
Medical subject headings
- Bacterial Proteins
- Cations, Divalent
- Gene Expression Regulation, Bacterial
- Hydrogen-Ion Concentration
- Salmonella typhimurium
- Virulence Factors