A Potential Combination Therapy of Berberine Hydrochloride With Antibiotics Against Multidrug-Resistant Acinetobacter baumannii.
A Potential Combination Therapy of Berberine Hydrochloride With Antibiotics Against Multidrug-Resistant Acinetobacter baumannii.
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DOI：
10.3389/fcimb.2021.660431
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发表时间：
2021
影响因子：
5.7
通讯作者：
Huang H
中科院分区：
文献类型：
--
作者：
Li X;Song Y;Wang L;Kang G;Wang P;Yin H;Huang H
多药耐药鲍曼不动杆菌可导致重症监护病房的严重感染，并对现有抗生素的最后手段迅速产生抗药性，对卫生保健系统构成重大全球威胁。盐酸小檗碱(BBH)是从黄连等植物中提取的一种异喹啉生物碱，因其可靠的治疗效果而被广泛用作抗菌药物。测定BBH与抗生素对多药耐药鲍曼不动杆菌的体外协同作用。单药对多药耐药鲍曼不动杆菌有较弱的抗菌活性(最低抑菌浓度≥为256 mg/L)。然而，它显著增加了耐多药菌株对FICI值为-0.5的抗生素的敏感性，甚至逆转了它们对抗生素(如替吉环素、舒巴坦、美罗培南和环丙沙星)的耐药性。体内研究表明，在中性粒细胞减少的小鼠大腿感染模型中，舒巴坦联合BBH具有比单一治疗更强的抗菌效率。并对BBH的抗菌增敏作用机制进行了评价。BBH促进ADEB基因的表达，并与ADEB转运蛋白结合，导致BBH摄取减少，这可能有助于减少ADEB泵对抗生素的排泄。ADEB基因敲除增加了MDR菌株对BBH的摄取，降低了抗生素的敏感性和与BBH的协同作用。总之，BBH有效地使这种MDR病原体对一系列由于抗生素耐药性而几乎不起作用的抗生素重新敏感，这表明BBH可能是一种有前途的治疗辅助候选药物来对抗MDR鲍曼不动杆菌。
Multidrug-resistant (MDR) Acinetobacter baumannii strains can cause severe infections in intensive care units, and are rapidly developing resistance to the last-resort of existing antibiotics, posing a major global threat to health care system. Berberine hydrochloride (BBH), a kind of isoquinoline alkaloids extracted from Berberis and other plants, has been widely used as an antibacterial medicine for its reliable therapeutic efficiency. The in vitro synergistic effects of BBH with antibiotics against MDR A. baumannii were determined. BBH alone had weak antimicrobial activity (e.g., MIC≥256 mg/L) against MDR A. baumannii. However, it dramatically increased the susceptibility of MDR strains against antibiotics with FICI values <0.5, even reversed their resistance to antibiotics (e.g., tigecycline, sulbactam, meropenem and ciprofloxacin). In vivo study has suggested BBH with sulbactam had stronger antimicrobial efficiency than monotherapy in a neutropenic murine thigh infection model. The antibiotic-sensitizing mechanism of action of BBH was evaluated as well. BBH boosted adeB gene expression and bound to the AdeB transporter protein, resulting in low uptake of BBH, which may contribute to less extrusion of antibiotics by the AdeABC pump. Knockout of the adeB gene increased uptake of BBH and diminished the antibiotic sensitization and synergistic effects between antibiotics and BBH in MDR strains. Together, BBH effectively re-sensitizes this MDR pathogen to a range of antibiotics that have become barely effective due to antibiotic resistance, which indicates BBH may be a promising therapeutic adjuvant candidate to combat MDR A. baumannii.