A genetic strategy to identify targets for the development of drugs that prevent bacterial persistence

• DOI: 10.1073/pnas.1315860110
• Publication Date: 2013-11-05T01:58:48Z
• Authors: Jee-Hyun Kim; Kathryn M. O’Brien; Ritu Sharma; Helena I. M. Boshoff; German Rehren; Sumit Chakraborty; Joshua B. Wallach; Mercedes Monteleone; Daniel J. Wilson; Courtney C. Aldrich; Clifton E. Barry; Kyu Y. Rhee; Sabine Ehrt; Dirk Schnappinger
• Keywords: Drug Development

Significance Chronic bacterial infections, such as those caused by Mycobacterium tuberculosis ( Mtb ), continue to claim the lives of millions people. New antibiotics are needed treat these but their development is hindered a lack targets whose inhibition quickly eradicates pathogens and prevents survival drug-tolerant persisters. We describe unique dual-control (DUC) switch that combines repression transcription controlled proteolysis silence gene activities in . By conditionally inactivating ’s nicotinamide adenine dinucleotide synthetase, we demonstrate DUC can identify proteins this pathogen requires for growth nonreplicating persistence vitro during infections. Targeting holds promise yielding drugs shorten duration antibacterial chemotherapies.