NDLI: Acidic pH and divalent cation sensing by PhoQ are dispensable for systemic salmonellae virulence

Content Provider	PubMed Central
Author	Hicks, Kevin G. Delbecq, Scott P. Enea, Sancho-vaello Blanc, Marie-pierre Dove, Katja K. Prost, Lynne R. Daley, Margaret E. Kornelius, Zeth Klevit, Rachel E. Miller, Samuel I.
Editor	Shao, Feng
Copyright Year	2015
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. 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.
Related Links	http://dx.doi.org/10.7554/elife.06792
Starting Page	6792
File Format	PDF
ISSN	2050084X
e-ISSN	2050084X
Journal	eLife
Volume Number	4
Language	English
Publisher	eLife Sciences Publications, Ltd
Publisher Date	2015-05-01
Access Restriction	Open
Rights Holder	eLife Sciences Publications, Ltd
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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