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Targeting lipid esterases in Mycobacteria grown under different physiological conditions using activity-based profiling with tetrahydrolipstatin (THL)

Ravindran, Madhu Sudhan and Rao, Srinivasa P. S. and Cheng, Xiamin and Shukla, Ankit and Cazenave-Gassiot, Amaury and Yao, Shao Q. and Wenk, Markus R.. (2014) Targeting lipid esterases in Mycobacteria grown under different physiological conditions using activity-based profiling with tetrahydrolipstatin (THL). Molecular & cellular proteomics, Vol. 13, H. 2. pp. 435-448.

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Official URL: http://edoc.unibas.ch/dok/A6233657

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Abstract

Tetrahydrolipstatin (THL) is bactericidal but its precise target spectrum is poorly characterized. Here, we used a THL analog and activity-based protein profiling to identify target proteins after enrichment from whole cell lysates of Mycobacterium bovis Bacillus Calmette-Guérin cultured under replicating and non-replicating conditions. THL targets α/β-hydrolases, including many lipid esterases (LipD, G, H, I, M, N, O, V, W, and TesA). Target protein concentrations and total esterase activity correlated inversely with cellular triacylglycerol upon entry into and exit from non-replicating conditions. Cellular overexpression of lipH and tesA led to decreased THL susceptibility thus providing functional validation. Our results define the target spectrum of THL in a biological species with particularly diverse lipid metabolic pathways. We furthermore derive a conceptual approach that demonstrates the use of such THL probes for the characterization of substrate recognition by lipases and related enzymes.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Molecular Immunology (Pluschke)
UniBasel Contributors:Wenk, Markus
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:The American Society for Biochemistry and Molecular Biology
ISSN:1535-9484
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:15 Aug 2014 07:16
Deposited On:15 Aug 2014 07:16

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