Acinetobacter baumannii, a leading cause of nosocomial infections, is a serious health threat. Limited therapeutic options due to multi-drug resistance and tolerance due to persister cells have urged the scientific community to develop new strategies to combat infections caused by this pathogen effectively. Since combination antibiotic therapy is an attractive strategy, the effect of combinations of antibiotics, belonging to four classes, was investigated on eradication of persister cells in A. baumannii. Among the antibiotics included in the study, tobramycin-based combinations were found to be the most effective. Tobramycin, in combination with colistin or ciprofloxacin, eradicated persister cells in A. baumannii in late exponential and stationary phases of growth. Mechanistically, colistin facilitated the entry of tobramycin into cells by increasing membrane permeability and inducing hyperpolarization of the inner membrane accompanied by increase in ROS production. Expression of the genes encoding universal stress protein and efflux pumps was down-regulated in response to tobramycin and colistin, suggesting increased lethality of their combination that might be responsible for eradication of persister cells. Thus, a combination of tobramycin and colistin could be explored as a promising option for preventing the relapse of A. baumannii infections due to persister cells.

鲍曼不动杆菌是院内感染的主要原因，是严重的健康威胁。由于多药耐药性和持久性细胞的耐受性导致的治疗选择有限，这促使科学界制定新的策略来有效对抗由这种病原体引起的感染。由于联合抗生素治疗是一种有吸引力的策略，因此研究了属于四类抗生素的组合对根除鲍曼不动杆菌中持久细胞的影响。在研究中包括的抗生素中，发现基于妥布霉素的组合是最有效的。妥布霉素与粘菌素或环丙沙星联合使用可根除鲍曼不动杆菌中的持久细胞在指数增长后期和稳定期。从机制上讲，粘菌素通过增加膜通透性和诱导内膜超极化并伴随 ROS 产生增加来促进妥布霉素进入细胞。响应妥布霉素和粘菌素，编码通用应激蛋白和外排泵的基因的表达被下调，表明它们组合的致死性增加，这可能是根除持久细胞的原因。因此，可以探索妥布霉素和粘菌素的组合作为预防鲍曼不动杆菌感染复发的有希望的选择。