粘菌素
鲍曼不动杆菌
微生物学
药理学
抗菌剂
碘化丙啶
溶血
维拉帕米
抗生素
罗丹明123
多重耐药
医学
生物
细菌
细胞凋亡
免疫学
程序性细胞死亡
内科学
铜绿假单胞菌
生物化学
遗传学
钙
作者
Sichen Liu,Huijing Zhou,Jingchun Kong,Huanchang Chen,Lei Chen,Miran Tang,Beibei Zhou,Mengxin Xu,Lijiang Chen,Tieli Zhou
标识
DOI:10.1016/j.ijantimicag.2024.107233
摘要
Acinetobacter baumannii, which is predominantly responsible for hospital-acquired infections, presents a tremendous clinical challenge due to its increasing antibiotic resistance to colistin (COL), a last-line antibiotic. As a result, the combination of antimicrobial and non-antimicrobial agents is emerging as a more popular treatment approach against infections caused by colistin-resistant (COL-R) A. baumannii. This study administered COL and verapamil (VER), i.e., an antihypertensive and antiarrhythmic agent. We found that the susceptibility of A. baumannii to COL was restored both in vitro and in vivo. Scanning electron microscope (SEM) and Crystal violet staining showed inhibition of the VER/COL combination on bacterial biofilm formation. Cytotoxicity assay and hemolysis test were used to confirm in vitro safety evaluation. Further experiments using propidium iodide (PI) staining revealed that the VER/COL combination improved the therapeutic efficacy of COL by modifying the permeability of bacterial membranes. As demonstrated by Reactive Oxygen Species (ROS) experiments, the drug combination caused the accumulation of bacterial ROS and their eventual death. Additionally, VER/COL treatment significantly reduced the efflux of Rhodamine 123 (Rh123). For the first time, this study identifies the anti-hypertensive drug VER as a COL potentiator against A. baumannii, providing a potential treatment approach against A. baumannii infections and improving patient outcomes.
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