S38: Chemical genetic profiling and discovery of kibdelomycin, a potent new class of bacterial type II topoisomerase inhibitor

The emergence of resistant strains of bacteria has led to an urgent need for new antibacterial agents.  To address this need we applied a chemical genetic assay in the bacterial pathogen Staphylococcus aureus to natural products screening.  This screening paradigm resulted in the discovery of Kibdelomycin, a novel class of antibiotics with broad spectrum gram positive antibacterial activity produced by a new member of the genus Kibdelosporangium.  Kibdelomycin is a potent inhibitor of DNA synthesis and is the first truly novel bacterial type-II topoisomerase inhibitor with potent antibacterial activity discovered from natural product sources in a long time. The chemical genetic assay, its application in the discovery of kibdelomycin and characterization of kibdelomycin will be discussed.