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Tandem tyrosine phosphosites in the Enteropathogenic Escherichia coli chaperone CesT are required for differential type III effector translocation and virulence.
Runte, Cameron S; Jain, Umang; Getz, Landon J; Secord, Sabrina; Kuwae, Asaomi; Abe, Akio; LeBlanc, Jason J; Stadnyk, Andrew W; Kaper, James B; Hansen, Anne-Marie; Thomas, Nikhil A.
Afiliación
  • Runte CS; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
  • Jain U; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
  • Getz LJ; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
  • Secord S; Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
  • Kuwae A; Laboratory of Bacterial Infection, Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
  • Abe A; Laboratory of Bacterial Infection, Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
  • LeBlanc JJ; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
  • Stadnyk AW; Department of Medicine, Division of Infectious Diseases, Dalhousie University, Halifax, Nova Scotia, Canada.
  • Kaper JB; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
  • Hansen AM; Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
  • Thomas NA; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
Mol Microbiol ; 108(5): 536-550, 2018 06.
Article en En | MEDLINE | ID: mdl-29509331
Enteropathogenic Escherichia coli (EPEC) use a type 3 secretion system (T3SS) for injection of effectors into host cells and intestinal colonization. Here, we demonstrate that the multicargo chaperone CesT has two strictly conserved tyrosine phosphosites, Y152 and Y153 that regulate differential effector secretion in EPEC. Conservative substitution of both tyrosine residues to phenylalanine strongly attenuated EPEC type 3 effector injection into host cells, and limited Tir effector mediated intimate adherence during infection. EPEC expressing a CesT Y152F variant were deficient for NleA effector expression and exhibited significantly reduced translocation of NleA into host cells during infection. Other effectors were observed to be dependent on CesT Y152 for maximal translocation efficiency. Unexpectedly, EPEC expressing a CesT Y153F variant exhibited significantly enhanced effector translocation of many CesT-interacting effectors, further implicating phosphosites Y152 and Y153 in CesT functionality. A mouse infection model of intestinal disease using Citrobacter rodentium revealed that CesT tyrosine substitution variants displayed delayed colonization and were more rapidly cleared from the intestine. These data demonstrate genetically separable functions for tandem tyrosine phosphosites within CesT. Therefore, CesT via its C-terminal tyrosine phosphosites, has relevant roles beyond typical type III secretion chaperones that interact and stabilize effector proteins.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Organofosfatos / Polímeros / Chaperonas Moleculares / Proteínas de Escherichia coli / Factores de Virulencia / Infecciones por Escherichia coli / Escherichia coli Enteropatógena Tipo de estudio: Prognostic_studies Idioma: En Revista: Mol Microbiol Asunto de la revista: BIOLOGIA MOLECULAR / MICROBIOLOGIA Año: 2018 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Organofosfatos / Polímeros / Chaperonas Moleculares / Proteínas de Escherichia coli / Factores de Virulencia / Infecciones por Escherichia coli / Escherichia coli Enteropatógena Tipo de estudio: Prognostic_studies Idioma: En Revista: Mol Microbiol Asunto de la revista: BIOLOGIA MOLECULAR / MICROBIOLOGIA Año: 2018 Tipo del documento: Article