Antibiotic Korormicin A Kills Bacteria by Producing Reactive Oxygen Species

As multidrug antibiotic resistance in pathogenic bacteria continues to rise, there is a critical need for novel antimicrobial agents. An essential requirement for a useful antibiotic is that it selectively targets bacteria without significant effects on the eukaryotic hosts. Korormicin is an excellent candidate in this respect because it targets a unique respiratory enzyme found only in prokaryotes, the Na+ -pumping NADH:quinone oxidoreductase (Na+ -NQR). Korormicin is synthesized by some species of the marine bacteriumPseudoalteromonas and is a potent and specific inhibitor of Na+ -NQR, an enzyme that is essential for the survival and proliferation of many Gram-negative human pathogens, includingVibrio cholerae andPseudomonas aeruginosa , among others. Here, we identified how korormicin selectively kills these bacteria. The binding of korormicin to Na+ -NQR promotes the formation of reactive oxygen species generated by the reaction of the FAD and the 2Fe-2S center cofactors with O2 .