Combination of pantothenamides with vanin inhibitors as a novel antibiotic strategy against gram-positive bacteria.

ABSTRACT: The emergence of resistance against current antibiotics calls for the development of new compounds to treat infectious diseases. Synthetic pantothenamides are pantothenate analogs that possess broad-spectrum antibacterial activity in vitro in minimal media. Pantothenamides were shown to be substrates of the bacterial coenzyme A (CoA) biosynthetic pathway, causing cellular CoA depletion and interference with fatty acid synthesis. In spite of their potential use and selectivity for bacterial metabolic routes, these compounds have never made it to the clinic. In the present study, we show that pantothenamides are not active as antibiotics in the presence of serum, and we found that they were hydrolyzed by ubiquitous pantetheinases of the vanin family. To address this further, we synthesized a

SUBMITTER: Jansen PA 

PROVIDER: S-EPMC3811400 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature