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Systematic Survey of Serine Hydrolase Activity in Mycobacterium tuberculosis Defines Changes Associated with Persistence.
Ortega, Corrie; Anderson, Lindsey N; Frando, Andrew; Sadler, Natalie C; Brown, Robert W; Smith, Richard D; Wright, Aaron T; Grundner, Christoph.
Afiliación
  • Ortega C; Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), Seattle, WA 98109, USA.
  • Anderson LN; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Frando A; Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA.
  • Sadler NC; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Brown RW; Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), Seattle, WA 98109, USA.
  • Smith RD; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Wright AT; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA. Electronic address: aaron.wright@pnnl.gov.
  • Grundner C; Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA. Electronic address: christoph.grundner@cidresearch.org.
Cell Chem Biol ; 23(2): 290-298, 2016 Feb 18.
Article en En | MEDLINE | ID: mdl-26853625
ABSTRACT
The transition from replication to non-replication underlies much of Mycobacterium tuberculosis (Mtb) pathogenesis, as non- or slowly replicating Mtb are responsible for persistence and poor treatment outcomes. Therapeutic targeting of non-replicating populations is a priority for tuberculosis treatment, but few drug targets in non-replicating Mtb are currently known. Here, we directly measured the activity of the highly diverse and druggable serine hydrolases (SHs) during active replication and non-replication using activity-based proteomics. We predict SH activity for 78 proteins, including 27 proteins with unknown function, and identify 37 SHs that remain active in the absence of replication, providing a set of candidate persistence targets. Non-replication was associated with major shifts in SH activity. These activity changes were largely independent of SH abundance, indicating extensive post-translational regulation of SHs. By probing a large cross-section of druggable Mtb enzyme space during replication and non-replication, we identify new SHs and suggest new persistence targets.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Serina / Farmacorresistencia Bacteriana / Hidrolasas / Mycobacterium tuberculosis Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Cell Chem Biol Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Serina / Farmacorresistencia Bacteriana / Hidrolasas / Mycobacterium tuberculosis Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Cell Chem Biol Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos