Aerocavin Is an Antibiotic with Potent and Specific Anti-Neisserial Activity.

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