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Lack of Specificity of Phenotypic Screens for Inhibitors of the Mycobacterium tuberculosis FAS-II System.
Grzegorzewicz, Anna E; Lelièvre, Joël; Esquivias, Jorge; Angala, Bhanupriya; Liu, Jiuyu; Lee, Richard E; McNeil, Michael R; Jackson, Mary.
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  • Grzegorzewicz AE; Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA.
  • Lelièvre J; Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
  • Esquivias J; Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
  • Angala B; Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
  • Liu J; Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA.
  • Lee RE; Department of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • McNeil MR; Department of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Jackson M; Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA.
Antimicrob Agents Chemother ; 65(1)2020 12 16.
Article en En | MEDLINE | ID: mdl-33139282
Phenotypic screening of inhibitors of the essential Mycobacterium tuberculosis FAS-II dehydratase HadAB led to the identification of GSK3011724A, a compound previously reported to inhibit the condensation step of FAS-II. Whole-cell-based and cell-free assays confirmed the lack of activity of GSK3011724A against the dehydratase despite evidence of cross-resistance between GSK3011724A and HadAB inhibitors. The nature of the resistance mechanisms is suggestive of alterations in the FAS-II interactome reducing access of GSK3011724A to KasA.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mycobacterium tuberculosis Idioma: En Revista: Antimicrob Agents Chemother Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mycobacterium tuberculosis Idioma: En Revista: Antimicrob Agents Chemother Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos