PhoQ对酸性pH值和二价阳离子的感知对于全身性沙门氏菌的毒力来说并非必需。
Acidic pH and divalent cation sensing by PhoQ are dispensable for systemic salmonellae virulence.
作者信息
Hicks Kevin G, Delbecq Scott P, Sancho-Vaello Enea, Blanc Marie-Pierre, Dove Katja K, Prost Lynne R, Daley Margaret E, Zeth Kornelius, Klevit Rachel E, Miller Samuel I
机构信息
Department of Microbiology, University of Washington Medical School, Seattle, United States.
Department of Biochemistry, University of Washington Medical School, Seattle, United States.
出版信息
Elife. 2015 May 23;4:e06792. doi: 10.7554/eLife.06792.
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.
鼠伤寒沙门氏菌PhoQ是一种具有周质传感器结构域（PD）的组氨酸激酶，它通过检测巨噬细胞吞噬体来促进毒力。PhoQ的活性受到二价阳离子的抑制，并在酸性pH值、二价阳离子有限以及阳离子抗菌肽（CAMP）的环境中被诱导。以前，尚不清楚沙门氏菌感知哪些信号来促进PhoQ介导的毒力。我们定义了在暴露于酸性pH值时PhoQ PD中产生的构象变化，这表明α螺旋4和5中诱导了结构灵活性，表明该区域有助于pH感应。因此，我们在PhoQ PD中的W104C和A128C之间设计了一个二硫键，以限制α螺旋4和5中的构象灵活性。PhoQ（W104C-A128C）对CAMP有反应，但被酸性pH值和二价阳离子限制抑制激活。携带phoQ（W104C-A128C）的鼠伤寒沙门氏菌在小鼠中具有毒力，这表明PhoQ对酸性pH值和二价阳离子的感应对于毒力来说是可有可无的。
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