Acinetobacter baumannii, a major pathogen that causes nosocomial infections, exhibits drug resistance. Efflux pumps are critical in developing multidrug resistance. Berberine hydrochloride exhibited inhibitory effects against bacteria and toxins, demonstrating antibacterial efficacy. However, there is limited research on berberine hydrochloride combined with multiple antibiotics through regulation of efflux pumps in multidrug-resistant A. baumannii. We evaluated the antibacterial effect of berberine hydrochloride in combination with multiple antibiotics, explored the resistance mechanisms regulated by efflux pumps, and analyzed the differential expression of active efflux pump genes (adeR, adeS, adeJ, adeM, adeG, and adeB) before and after berberine hydrochloride exposure, to provide new therapeutic strategies for managing multidrug-resistant A. baumannii infections. One hundred non-repetitive A. baumannii strains were isolated from patients with respiratory infections. The microdilution method was used for the determination of minimal inhibitory concentration (MIC) and the checkerboard method for the determination of the fractional inhibitory concentration (FIC) index. Reverse transcription polymerase chain reaction quantified efflux pump gene expression in sensitive and resistant strains before and after berberine hydrochloride treatment. Strains showing significant differences were selected for transcriptomic sequencing. Berberine hydrochloride showed synergistic effects with nine antibiotics, the strongest being amikacin, meropenem, and cefepime. Resistance reversal occurred especially with levofloxacin. adeJ and adeB expression differed significantly between sensitive and resistant strains. Berberine hydrochloride induced notable changes in adeS, adeG, adeB, and adeR. Transcriptome sequencing revealed the significant expression of adeA, adeN, and adeT2. Berberine hydrochloride enhances antibiotic sensitivity and reverses resistance by regulating efflux pump gene expression, providing a theoretical foundation for improved treatment.IMPORTANCEThis study investigates multidrug-resistant Acinetobacter baumannii (MDRAB) strains isolated from clinical infections using the microplate dilution method to evaluate the antibacterial efficacy of berberine in combination with various antibiotics. The research simultaneously analyzes the differential expression levels of active efflux pump genes before and after berberine treatment. The findings aim to identify novel therapeutic strategies for MDRAB, explore the drug resistance mechanisms mediated by efflux pumps in AB, and elucidate berberine's role in reversing AB resistance through efflux pump regulation. These insights provide theoretical foundations for improving cure rates in MDRAB-infected patients and advancing drug target design.
Wang et al. (Tue,) studied this question.