Discovery and characterization of natural tropolones as inhibitors of the antibacterial target CapF from Staphylococcus aureus.

ABSTRACT: The rapid spread of antibiotic-resistance among pathogenic bacteria poses a serious risk for public health. The search for novel therapeutic strategies and antimicrobial compounds is needed to ameliorate this menace. The bifunctional metalloenzyme CapF is an antibacterial target produced by certain pathogenic bacteria essential in the biosynthetic route of capsular polysaccharide, a mucous layer on the surface of bacterium that facilitates immune evasion and infection. We report the first inhibitor of CapF from Staphylococcus aureus, which was identified by employing fragment-based methodologies. The hit compound 3-isopropenyl-tropolone inhibits the first reaction catalyzed by CapF, disrupting the synthesis of a key precursor of capsular polysaccharide. Isothermal titration calorimetry dem

SUBMITTER: Nakano K 

PROVIDER: S-EPMC5393024 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature