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抗生素耐药性与抗菌肽的设计:克服微生物耐药性的策略。

The Resilience of to Antibiotics and the Designing of Antimicrobial Peptides to Overcome Microbial Resistance.

机构信息

Centro de Investigación en Biotecnología, Universidad Autónoma del Estado de Morelos CEIB-UAEM. Av. Universidad No. 1001, Col Chamilpa, C.P. 62209, Cuernavaca, Morelos, México.

Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Av. Ciudad Universitaria 3000, C.P. 04510, Coyoacán, Ciudad de México, México.

出版信息

Curr Med Chem. 2022;30(1):72-103. doi: 10.2174/0929867329666220907100505.

Abstract

Pseudomonas aeruginosa (P. aeruginosa) is a bacterium of medical concern known for its potential to persist in diverse environments due to its metabolic capacity. Its survival ability is linked to its relatively large genome of 5.5-7 Mbp, from which several genes are employed in overcoming conventional antibiotic treatments and promoting resistance. The worldwide prevalence of antibiotic-resistant clones of P. aeruginosa necessitates novel approaches to researching their multiple resistance mechanisms, such as the use of antimicrobial peptides (AMPs). In this review, we briefly discuss the epidemiology of the resistant strains of P. aeruginosa and then describe their resistance mechanisms. Next, we explain the biology of AMPs, enlist the present database platforms that describe AMPs, and discuss their usefulness and limitations in treating P. aeruginosa strains. Finally, we present 13 AMPs with theoretical action against P. aeruginosa, all of which we evaluated in silico in this work. Our results suggest that the AMPs we evaluated have a carpet-like mode of action with a membranolytic function in Gram-positive and Gramnegative bacteria, with a clear potential of synthesis for in vitro evaluation.

摘要

铜绿假单胞菌(P. aeruginosa)是一种医学相关的细菌,由于其代谢能力,它能够在各种环境中持续存在。它的生存能力与其相对较大的 5.5-7 Mbp 基因组有关,其中一些基因被用于克服传统抗生素治疗并促进耐药性。铜绿假单胞菌的抗生素耐药克隆在全球范围内普遍存在,这就需要采用新的方法来研究其多种耐药机制,例如使用抗菌肽 (AMPs)。在这篇综述中,我们简要讨论了耐药铜绿假单胞菌菌株的流行病学,然后描述了它们的耐药机制。接下来,我们解释了 AMPs 的生物学特性,列出了目前描述 AMPs 的数据库平台,并讨论了它们在治疗铜绿假单胞菌菌株方面的有用性和局限性。最后,我们提出了 13 种针对铜绿假单胞菌的理论作用的 AMPs,我们在这项工作中都进行了计算机模拟评估。我们的结果表明,我们评估的 AMPs 具有地毯样作用模式,对革兰氏阳性和革兰氏阴性细菌具有膜溶解功能,具有明确的体外评估合成潜力。

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