Hiren V. Patel
B.A. Boston University, 2010
5th Year MSTP
3rd Year Molecular Genetics & Microbiology Graduate Student
Advisor: Jessica Seeliger, PhD
Department: Pharmacological Sciences, Stony Brook University
Graduate Program: Molecular Genetics & Microbiology
Title: Towards the inhibition & functional characterization of hydrolase enzymes in mycobacteria
Abstract :
Hiren V. Patel and Jessica C. Seeliger
With the emergence of multiple and extremely drug-resistant strains of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) in humans, drugs that inhibit multiple targets have the potential to improve the treatment of active and latent Mtb infections. The serine hydrolase (SH) family of enzymes consists of proteases, esterases, lipases, and acyltransferases that use a nucleophilic serine residue for catalysis. In Mtb, many SHs have essential functions for Mtb survival, which makes the SH family a promising candidate for drug screening. Using a systems-level approach, the SH proteomes were visualized in two species,
M. smegmatis (non-pathogenic) and M. marinum (pathogenic), which serve as models for Mtb. Distinct populations of proteins in the cell envelope, cytosol, and culture filtrate of M. smegmatis and M. marinum were visualized by fluorescence. Furthermore, pre-treatment of M. marinum lysates with known SH inhibitors phenylmethylsulfonyl fluoride or tetrahydrolipstatin showed concentration-dependent inhibition of selected serine hydrolases. Taken together, a systems-level approach in M. smegmatis and M. marinum suggests that a similar strategy in Mtb will aid in characterizing the SH family and screening the SH proteome with small-molecule libraries. Therefore, we plan to identify SHs in subcellular locations in Mtb and identify small-molecule inhibitors that will aid in the functional characterization of SHs in M. marinum and Mtb.
Awards:
NIH NRSA F30
