Acidic pH and divalent cation sensing by PhoQ are dispensable for systemic salmonellae virulence.
Elife
; 4: e06792, 2015 May 23.
Article
em En
| MEDLINE
| ID: mdl-26002083
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. 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Salmonella typhimurium
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Proteínas de Bactérias
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Cátions Bivalentes
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Regulação Bacteriana da Expressão Gênica
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Fatores de Virulência
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Concentração de Íons de Hidrogênio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Elife
Ano de publicação:
2015
Tipo de documento:
Article