铜绿假单胞菌
微生物学
化学
抗生素
多粘菌素
多重耐药
细菌
体内
药理学
医学
生物
生物技术
遗传学
作者
Taotao Lu,Xinyu Zheng,Fei Mao,Qiao Cao,Qin Cao,Jin Zhu,Xiaokang Li,Lefu Lan,Baoli Li,Jian Li
标识
DOI:10.1016/j.ejmech.2022.114318
摘要
Pseudomonas aeruginosa (P. aeruginosa) DK2 is a multidrug-resistant (MDR) gram-negative bacterial pathogen, being observed serious resistance to the 'last-resort' antibiotic, polymyxin B (PB). Combination therapies with adjuvants have emerged as effective strategies to reactivate the antibiotics resisted by MDR bacteria. Herein, we screened a library of approved drugs and found that niclosamide (NIC), an anthelmintic drug, could potentiate the efficacy of PB against MDR P. aeruginosa DK2. Next, a series of novel NIC-derived adjuvants were designed, synthesized, and evaluated the synergistic activity with PB. Among them, the combination of 15 with PB displayed superior elimination of P. aeruginosa DK2 in vitro and in vivo compared with the single administration. Moreover, this combination decelerated PB-resistance progress in DK2, along with lower potential toxicity. Overall, this study provides a strategy for development antibiotic adjuvants to potentiate PB against MDR P. aeruginosa infections.
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