Systematic Survey of Serine Hydrolase Activity in Mycobacterium tuberculosis Defines Changes Associated with Persistence.
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.
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