TY - JOUR TI - Acidic pH and divalent cation sensing by PhoQ are dispensable for systemic salmonellae virulence AU - Hicks, Kevin G AU - Delbecq, Scott P AU - Sancho-Vaello, Enea AU - Blanc, Marie-Pierre AU - Dove, Katja K AU - Prost, Lynne R AU - Daley, Margaret E AU - Zeth, Kornelius AU - Klevit, Rachel E AU - Miller, Samuel I A2 - Shao, Feng VL - 4 PY - 2015 DA - 2015/05/23 SP - e06792 C1 - eLife 2015;4:e06792 DO - 10.7554/eLife.06792 UR - https://doi.org/10.7554/eLife.06792 AB - 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. PhoQW104C-A128C is responsive to CAMP, but is inhibited for activation by acidic pH and divalent cation limitation. phoQW104C-A128C Salmonella enterica Typhimurium is virulent in mice, indicating that acidic pH and divalent cation sensing by PhoQ are dispensable for virulence. KW - Salmonella KW - bacterial pathogenesis KW - intracellular virulence KW - innate immunity KW - signal transduction KW - sensor kinase JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -