Slow-onset inhibition of the FabI enoyl reductase from francisella tularensis: residence time and in vivo activity.

ABSTRACT: Francisella tularensis is a highly virulent and contagious Gram-negative intracellular bacterium that causes the disease tularemia in mammals. The high infectivity and the ability of the bacterium to survive for weeks in a cool, moist environment have raised the possibility that this organism could be exploited deliberately as a potential biological weapon. Fatty acid biosynthesis (FAS-II) is essential for bacterial viability and has been validated as a target for the discovery of novel antibacterials. The FAS-II enoyl reductase ftuFabI has been cloned and expressed, and a series of diphenyl ethers have been identified that are subnanomolar inhibitors of the enzyme with MIC90 values as low as 0.00018 microg mL(-1). The existence of a linear correlation between the Ki and MIC values strongl

SUBMITTER: Lu H 

PROVIDER: S-EPMC2693246 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature