盐酸小檗碱协同增强青霉素对产青霉素酶淋球菌的体外抗菌活性研究OA

Objective This study aimed to evaluate the synergistic effect of berberine hydro-chloride on the antibacterial activity of penicillin against Penicillinase-Producing Neisseria gonor-rhoeae(PPNG),offering new insights for the prevention and treatment of highly drug-resistant PPNG.Methods The minimum inhibitory concentration(MIC)of berberine hydrochloride com-bined with penicillin against PPNG strains were determined using microbroth dilution and checker-board assays,with fractional inhibitory concentration(FIC)indices calculated to assess antibacte-rial efficacy.TEM DNA mutations were detected via gene sequencing.TEM mRNA expression levels were measured by RT-qPCR.Penicillinase was extracted by ultrasonic disruption,and its activity was assessed using the dual-wavelength colorimetric Amplite assay kit.Results The MIC range of the berberine hydrochloride-only treatment against PPNG was 0.03～128 μg/mL.The MIC of penicillin decreased by ≥4-fold and the FIC index was ≤0.5 when berberine hydrochlo-ride was combined with penicillin against PPNG,demonstrating the synergistic antibacterial effects of these two compounds.The combined antibacterial strategy did not induce mutations in TEM genes,but it decreased penicillinase activity(P＜0.05)through downregulating the mRNA ex-pression of TEM(2-ΔΔCt＜1).Conclusions Berberine hydrochloride not only directly inhibits PPNG growth but also restores penicillin sensitivity by down-regulating TEM gene expression and inhibiting penicillinase activity.These findings showed that berberine hydrochloride is an antibiotic adjuvant against PPNG.