Abstract
OBJECTIVE: Neisseria gonorrhoeae (N. gonorrhoeae) is responsible for the sexually transmitted infection (STI) gonorrhea, which has an estimated global annual incidence of 82.4 million cases among adults. The recommended first-line treatment typically involves a single-dose systemic therapy, comprising injectable ceftriaxone and oral azithromycin. Nonetheless, the first-line treatment failures caused by antimicrobial resistance represent a major global public health concern, threatening the efficacy of current gonorrhea treatments and highlighting the urgent need for the development of alternative therapeutic approaches. METHODS: A total of 54 clinical strains of N. gonorrhoeae were collected in Nanchang City, 2021. To assess the efficacy of antibiotics and chelerythrine chloride, we determined the minimum inhibitory concentrations (MICs) using agar dilution and broth microdilution methods, respectively. To explicitly evaluate the potential for resistance induction, the ATCC49226 strain was subjected to continuous passaging for 30 days in sub-MIC concentrations of chelerythrine chloride, with MIC assessments every 5 days. RESULTS: In clinical samples, antimicrobial resistance was observed for penicillin (67.27%), tetracycline (81.82%), ciprofloxacin (98.18%), azithromycin (5.45%), and spectinomycin (0%), with decreased susceptibility for ceftriaxone (16.36%) and cefixime (20.00%). High-throughput screening of a natural product library identified chelerythrine chloride as exhibiting significant inhibitory activity against N. gonorrhoeae, including strains with decreased susceptibility to cephalosporins. The MIC range was 0.002-8 mg/L, with both the MIC(50) and MIC(90) values at 8 mg/L. Furthermore, N. gonorrhoeae did not develop resistance, maintaining a stable MIC of 4 mg/L over a 30-day treatment period. CONCLUSION: In this study, we have established a novel association between chelerythrine chloride and N. gonorrhoeae, demonstrating for the first time its preliminary efficacy in eradicating multidrug-resistant strains of N. gonorrhoeae. Considering the significant resistance challenges posed by N. gonorrhoeae. chelerythrine chloride emerges as a promising antibacterial agent with substantial potential for clinical development.