Title : Systematic Survey of Serine Hydrolase Activity in Mycobacterium tuberculosis Defines Changes Associated with Persistence - Ortega_2016_Cell.Chem.Biol_23_290 |
Author(s) : Ortega C , Anderson LN , Frando A , Sadler NC , Brown RW , Smith RD , Wright AT , Grundner C |
Ref : Cell Chemical Biology , 23 :290 , 2016 |
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. |
PubMedSearch : Ortega_2016_Cell.Chem.Biol_23_290 |
PubMedID: 26853625 |
Ortega C, Anderson LN, Frando A, Sadler NC, Brown RW, Smith RD, Wright AT, Grundner C (2016)
Systematic Survey of Serine Hydrolase Activity in Mycobacterium tuberculosis Defines Changes Associated with Persistence
Cell Chemical Biology
23 :290
Ortega C, Anderson LN, Frando A, Sadler NC, Brown RW, Smith RD, Wright AT, Grundner C (2016)
Cell Chemical Biology
23 :290