Discovery of synergistic activity of fluoroquinolones in combination with antimicrobial peptides against clinical polymyxin-resistant Pseudomonas aeruginosa DK2
Discovery of synergistic activity of fluoroquinolones in combination with antimicrobial peptides against clinical polymyxin-resistant Pseudomonas aeruginosa DK2
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发现氟喹诺酮类药物与抗菌肽联合对抗临床耐多粘菌素铜绿假单胞菌 DK2 的协同活性
DOI：
10.1016/j.cclet.2019.07.063
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发表时间：
2020-02
影响因子：
9.1
通讯作者：
Jian Li
中科院分区：
文献类型：
--
作者：
Xinyu Zheng;Qiao Cao;Qin Cao;Fei Mao;Xiaokang Li;Jin Zhu;Lefu Lan;Jian Li
多粘菌素B（PB）作为革兰阴性菌多重耐药的最后一道防线，已引起对P的耐药性。最近在空中。幸运的是，协同治疗可以保留最后一类抗生素，减少耐药的发生。在这里，我们进行了970个批准的药物与PB协同抗P。铜绿假单胞菌DK2对PB严重耐药，MIC = 512 μg/mL。令人鼓舞的是，我们发现氟喹诺酮类药物可以与PB协同作用，并使PB的MIC明显降低至临床敏感折点（2 μg/mL）以下。尤其是吉美曲肽与PB的协同效应最高，导致MIC降低4096倍（从512 μg/mL降至0.125 μg/mL）。此外，在吉米福司和粘杆菌素的组合中也观察到协同效应。最后，外膜透性实验表明，吉非替尼可增加细菌细胞膜对P.这部分解释了协同作用的机理。这些结果表明，氟喹诺酮类药物是解决多粘菌素耐药感染新威胁的有吸引力的增效剂。
Polymyxin B (PB), as the last-line of defense against multidrug-resistant Gram-negative bacteria, has caused resistance toP. aeruginosarecently. Fortunately, synergistic treatment could preserve the last class of antibiotics and reduce the emergency of drug resistance. Here, we performed a screen of 970 approved drugs synergized with PB against theP. aeruginosaDK2, which is severely resistant to PB, MIC = 512 μg/mL. Encouragingly, we found fluoroquinolones could synergy with PB and achieved an obvious reduction in MIC of PB below the clinical susceptible breakpoint (2 μg/mL). Especially, gemifloxacin achieved the highest synergistic effect with PB, leading to a 4096-fold MIC reduction (reduced from 512 μg/mL to 0.125 μg/mL). Furthermore, synergistic effect was also observed in the combination of gemifloxacin and colistin. Finally, outer membrane permeabilization assay showed that gemifloxacin could increase the permeability of bacterial cell membranes forP. aeruginosawhich partly explained the synergy mechanism. These results indicate that fluoroquinolones represent attractive synergists to address the emerging threat of polymyxin-resistant infections.
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影响因子：
9.1
作者：
Meng Zhu;Peng Liu;Zhong-Wei Niu
通讯作者：
Zhong-Wei Niu
DOI：
10.1073/pnas.1018249108
发表时间：
2011-05-03
影响因子：
11.1
作者：
Yang, Lei;Jelsbak, Lars;Molin, Soren
通讯作者：
Molin, Soren
影响因子：
16.6
作者：
MacNair CR;Stokes JM;Carfrae LA;Fiebig-Comyn AA;Coombes BK;Mulvey MR;Brown ED
通讯作者：
Brown ED
影响因子：
9.1
作者：
Nagarajan, Sangaraiah;Shanmugavelan, Poovan;Shanmugaiah, Vellasamy
通讯作者：
Shanmugaiah, Vellasamy
影响因子：
4.9
作者：
Puzniak, Laura;DePestel, Daryl D.;Gupta, Vikas
通讯作者：
Gupta, Vikas