Acidic pH and divalent cation sensing by PhoQ are dispensable for systemic salmonellae virulence
- University of Washington Medical School, United States
- Universidad del País Vasco/Euskal Herriko Unibertsitatea, Spain
- University of Wisconsin-Madison, United States
- University of San Diego, United States
- Max-Planck-Institut für Entwicklungsbiologie, Germany
Abstract
Salmonellae 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 are virulent in mice, indicating that acidic pH and divalent cation sensing by PhoQ are dispensable for virulence.
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Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol (2982-02) of the University of Washington.
Copyright
© 2015, Hicks et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Acidic pH and divalent cation sensing by PhoQ are dispensable for systemic salmonellae virulence
eLife 4:e06792.
https://doi.org/10.7554/eLife.06792
