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Escape of intracellular Shigella from autophagy requires binding to cholesterol through the type III effector, IcsB.
Kayath, Christian Aimé; Hussey, Seamus; El hajjami, Nargisse; Nagra, Karan; Philpott, Dana; Allaoui, Abdelmounaaïm.
Afiliación
  • Kayath CA; Laboratoire de Bactériologie Moléculaire, Faculté de Médecine, Université Libre de Bruxelles, Brussels, Belgium.
Microbes Infect ; 12(12-13): 956-66, 2010 Nov.
Article en En | MEDLINE | ID: mdl-20599519
Type III secretion systems are present in many pathogenic bacteria and mediate the translocation of bacterial effectors into host cells. Identification of host targets of these effectors is crucial for understanding bacterial virulence. IcsB, a type III secretion effector, helps Shigella to evade the host autophagy defense system by binding to the autophagy protein, Atg5. Here, we show that IcsB is able to interact specifically with cholesterol. The cholesterol binding domain (CBD) of IcsB is located between residues 288 and 351. Specific mutations of single tyrosine residues Y297 or Y340 of IcsB by phenylalanine (F) slightly reduced cholesterol binding, whereas deletion of the entire CBD or double mutation Y297F-Y340F strongly abolished interactions with cholesterol. To determine whether Shigella expressing IcsB variants could evade autophagy as effectively as the wild-type Shigella, we infected MDAMC cells stably expressing the autophagy marker LC3 fused to GFP and bacterial autophagosome formation was quantified using fluorescence microscopy. Mutation Y297F or Y340F slightly impaired IcsB function, whereas complete removal of CBD or mutation Y297F-Y340F significantly impaired autophagy evasion. Furthermore, we report that BopA, the counterpart of IcsB in Burkholderia pseudomallei with similar autophagy-evading properties, contains the CBD domain and is also able to bind cholesterol.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Shigella flexneri / Autofagia / Proteínas Bacterianas / Colesterol / Factores de Virulencia / Interacciones Huésped-Patógeno Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Microbes Infect Asunto de la revista: ALERGIA E IMUNOLOGIA / MICROBIOLOGIA Año: 2010 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Francia

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Shigella flexneri / Autofagia / Proteínas Bacterianas / Colesterol / Factores de Virulencia / Interacciones Huésped-Patógeno Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Microbes Infect Asunto de la revista: ALERGIA E IMUNOLOGIA / MICROBIOLOGIA Año: 2010 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Francia