Gonorrhea remains a major global public health problem because of the high incidence of
infection (estimated 82 million cases in 2020) and the emergence and spread of Neisseria gonorrhoeae strains resistant to previous and current
antibiotics used to treat
infections. Given the dearth of new
antibiotics that are likely to enter clinical practice in the near future, there is concern that cases of untreatable
gonorrhea might emerge. In response to this crisis, the World Health Organization (WHO), in partnership with the Global
Antibiotic Research and Development Partnership (GARDP), has made the search for and development of new
antibiotics against N. gonorrhoeae a priority. Ideally, these
antibiotics should also be active against other sexually transmitted organisms, such as Chlamydia trachomatis and/or Mycoplasma genitalium, which are often found with N. gonorrhoeae as
co-infections.
Corallopyronin A is a potent antimicrobial that exhibits activity against Chlamydia spp. and inhibits transcription by binding to the RpoB switch region. Accordingly, we tested the effectiveness of
corallopyronin A against N. gonorrhoeae. We also examined the mutation frequency and modes of potential resistance against
corallopyronin A. We report that
corallopyronin A has potent antimicrobial action against
antibiotic-susceptible and
antibiotic-resistant N. gonorrhoeae strains and could eradicate gonococcal
infection of cultured, primary human cervical epithelial cells. Critically, we found that spontaneous
corallopyronin A-resistant mutants of N. gonorrhoeae are exceedingly rare (≤10-10) when selected at 4× the MIC. Our results support pre-clinical studies aimed at developing
corallopyronin A for gonorrheal treatment regimens. IMPORTANCE The high global incidence of
gonorrhea, the lack of a protective
vaccine, and the emergence of N. gonorrhoeae strains expressing resistance to currently used
antibiotics demand that new treatment options be developed. Accordingly, we investigated whether
corallopyronin A, an
antibiotic which is effective against other pathogens, including C. trachomatis, which together with gonococci frequently cause
co-infections in humans, could exert anti-gonococcal action in vitro and ex vivo, and potential resistance emergence. We propose that
corallopyronin A be considered a potential future treatment option for
gonorrhea because of its potent activity, low resistance development, and recent advances in scalable production.