Aerocavin is an antibiotic with potent and specific anti-Neisserial activity

Gonorrhea, caused by <i>N. gonorrhoeae</i> , is a widespread sexually transmitted disease that is becoming resistant to all currently used antibiotics. Therefore, new therapeutics against gonorrhea are desperately needed. Here, we show that a natural product - aerocavin, is highly potent and specific against <i>Neisseria</i> . Aerocavin accumulates in <i>N. gonorrhoeae</i> at high levels and inhibits bacterial RNA polymerase (RNAP) by binding the switch region. Aerocavin resistance mutations evolve in <i>N. gonorrhoeae</i> at a low rate and are absent in clinical isolates. Previously overlooked narrow-spectrum antimicrobials like aerocavin may enable microbiome-sparing treatments of gonorrhea.