Identification of new drug targets and resistance mechanisms in Mycobacterium tuberculosis.

ABSTRACT: Identification of new drug targets is vital for the advancement of drug discovery against Mycobacterium tuberculosis, especially given the increase of resistance worldwide to first- and second-line drugs. Because traditional target-based screening has largely proven unsuccessful for antibiotic discovery, we have developed a scalable platform for target identification in M. tuberculosis that is based on whole-cell screening, coupled with whole-genome sequencing of resistant mutants and recombineering to confirm. The method yields targets paired with whole-cell active compounds, which can serve as novel scaffolds for drug development, molecular tools for validation, and/or as ligands for co-crystallization. It may also reveal other information about mechanisms of action, such as activation o

SUBMITTER: Ioerger TR 

PROVIDER: S-EPMC3781026 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature