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

被引：26

作者：

Hicks, Kevin G. ^{[1
]}

Delbecq, Scott P. ^{[2
]}

Sancho-Vaello, Enea ^{[3
]}

Blanc, Marie-Pierre ^{[1
]}

Dove, Katja K. ^{[2
]}

Prost, Lynne R. ^{[4
]}

Daley, Margaret E. ^{[5
]}

Zeth, Kornelius ^{[6
,7
]}

Klevit, Rachel E. ^{[2
]}

Miller, Samuel I. ^{[1
,8
,9
]}

机构：

[1] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA

[2] Univ Washington, Sch Med, Dept Biochem, Seattle, WA 98195 USA

[3] Univ Basque Country, Euskal Herriko Unibertsitatea CSIC, Ctr Mixto Consejo Super Invest, UPV EHU,Unidad Biofis, Leioa, Bizkaia, Spain

[4] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA

[5] Univ San Diego, Dept Chem & Biochem, San Diego, CA 92110 USA

[6] Univ Basque Country, Dept Biochem & Mol Biol, Leioa, Spain

[7] Basque Res Org Sci, Ikerbasque, Bilbao, Spain

[8] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA

[9] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA

来源：

ELIFE | 2015年 / 4卷

关键词：

ENTERICA SEROVAR TYPHIMURIUM; BACTERIAL SENSOR KINASE; III SECRETION SYSTEM; ANTIMICROBIAL PEPTIDES; HISTIDINE KINASES; GENE-EXPRESSION; OUTER-MEMBRANE; RESISTANCE; MACROPHAGES; DOMAIN;

D O I：

10.7554/eLife.06792

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 alpha-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 alpha-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.

引用

页码：1 / 59

页数：23

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