Can octapeptin antibiotics combat extensively drug-resistant (XDR) bacteria?
Can octapeptin antibiotics combat extensively drug-resistant (XDR) bacteria?
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DOI：
10.1080/14787210.2018.1483240
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发表时间：
2018-06
影响因子：
5.7
通讯作者：
Cooper MA
中科院分区：
文献类型：
--
作者：
Blaskovich MAT;Pitt ME;Elliott AG;Cooper MA
八肽是环状脂肽家族，首次报道于 20 世纪 70 年代，但后来基本上被忽视。当时，他们报道的针对多粘菌素耐药细菌的抗生素活性令人好奇。如今，革兰氏阴性菌广泛耐药性的出现促使它们被“重新发现”。临床管道中新抗生素的缺乏加上抗生素耐药性在全球蔓延，特别是对美罗培南和多粘菌素 B 和 E（粘菌素）。我们回顾了八肽素的最初发现、它们最近的首次化学合成及其作用方式，然后讨论它们作为一类新型抗生素治疗广泛耐药 (XDR) 革兰氏阴性菌感染的潜力，并与密切相关的多粘菌素进行直接比较。临床使用的环状脂肽（多粘菌素抗生素）因其化学型而具有显着的剂量限制性肾毒性。这种毒性阻碍了改进的多粘菌素类似物进入临床，并损害了人们对脂肽抗生素的普遍看法。我们认为，八肽素与多粘菌素有根本不同，具有不同的作用模式、针对 MDR 和 XDR 细菌的作用谱以及优异的临床前安全性。它们代表了早期候选药物，可以帮助启动抗生素发现管道。
The octapeptins are a family of cyclic lipopeptides first reported in the 1970s then largely ignored. At the time, their reported antibiotic activity against polymyxin-resistant bacteria was a curiosity. Today the advent of widespread drug resistance in Gram-negative bacteria has prompted their ‘rediscovery’. The paucity of new antibiotics in the clinical pipeline is coupled with a global spread of increasing antibiotic resistance, particularly to meropenem and polymyxins B and E (colistin). We review the original discovery of octapeptins, their recent first chemical syntheses, and their mode of action, then discuss their potential as a new class of antibiotics to treat extensively drug resistant (XDR) Gram-negative infections, with direct comparisons to the closely related polymyxins. Cyclic lipopeptides in clinical use (polymyxin antibiotics) have significant dose-limiting nephrotoxicity inherent to their chemotype. This toxicity has prevented improved polymyxin analogs from progressing to the clinic, and tainted the perception of lipopeptide antibiotics in general. We argue that the octapeptins are fundamentally different from the polymyxins, with a disparate mode of action, spectra of action against MDR and XDR bacteria and a superior pre-clinical safety profile. They represent early stage candidates that can help prime the antibiotic discovery pipeline.
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影响因子：
120.1
作者：
Cook, David;Brown, Dearg;Pangalos, Menelas N.
通讯作者：
Pangalos, Menelas N.
抗菌八肽C4类似物活跃于加密环球物种。
影响因子：
4.9
作者：
Chitty JL;Butler MS;Suboh A;Edwards DJ;Cooper MA;Fraser JA;Robertson AAB
通讯作者：
Robertson AAB
影响因子：
4.9
作者：
Abdelraouf, Kamilia;Braggs, Kirk H.;Tam, Vincent H.
通讯作者：
Tam, Vincent H.
影响因子：
6.7
作者：
De Zoysa, Gayan Heruka;Glossop, Hugh Douglas;Sarojini, Vijayalekshmi
通讯作者：
Sarojini, Vijayalekshmi
DOI：
10.1016/j.ijantimicag.2016.06.023
发表时间：
2016-12-01
影响因子：
10.8
作者：
Baron, Sophie;Hadjadj, Linda;Olaitan, Abiola Olumuyiwa
通讯作者：
Olaitan, Abiola Olumuyiwa