Evaluation of Antibiotic Resistance Mechanisms in Gram-Negative Bacteria.
Evaluation of Antibiotic Resistance Mechanisms in Gram-Negative Bacteria.
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DOI：
10.3390/antibiotics12111590
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发表时间：
2023-11-03
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影响因子：
--
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中科院分区：
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多重耐药革兰氏阴性菌感染呈指数级增长，构成了最紧迫的全球医疗保健和经济威胁之一。由于缺乏新的治疗方法，世界卫生组织在2017年将这些细菌物种列为优先病原体，称为ESKAPE病原体。这种分类强调了迫切需要研究和开发新的靶向治疗。这些优先病原体中的大多数是革兰氏阴性菌，它们具有结构动态的细胞包膜，使它们能够抵抗多种抗生素，从而导致死亡率增加。尽管自WHO分类以来已经过去了6年，但在产生新的治疗想法方面取得的进展还不够，抗菌素耐药性继续升级，成为全球滴答作响的定时炸弹。已经采取了许多努力和策略，通过靶向特定的耐药机制来对抗抗生素耐药性水平的上升。这些机制包括抗生素失活/修饰酶，外膜孔蛋白重塑，增强外排泵作用和抗生素靶位点的改变。一些策略已经显示出临床前景，例如利用β-内酰胺酶抑制剂作为抗生素佐剂，以及最近在基于机器的学习中的进步，采用人工智能来促进新型窄谱抗生素的生产。然而，对抗生素耐药性发生的确切机制的进一步研究，特别是针对每种细菌物种的研究，可以为探索窄谱靶向治疗铺平道路。本文介绍了革兰阴性菌的主要特征和目前的治疗方法，重点介绍了大肠埃希菌、鲍曼不动杆菌、铜绿假单胞菌和肺炎克雷伯菌的主要耐药机制。此外，替代疗法的潜在方向将被讨论，沿着其相对的作用模式，提供了一个未来的观点和洞察力的学科抗菌素耐药性。
Multidrug-resistant Gram-negative bacterial infections are exponentially increasing, posing one of the most urgent global healthcare and economic threats. Due to the lack of new therapies, the World Health Organization classified these bacterial species as priority pathogens in 2017, known as ESKAPE pathogens. This classification emphasizes the need for urgent research and development of novel targeted therapies. The majority of these priority pathogens are Gram-negative species, which possess a structurally dynamic cell envelope enabling them to resist multiple antibiotics, thereby leading to increased mortality rates. Despite 6 years having passed since the WHO classification, the progress in generating new treatment ideas has not been sufficient, and antimicrobial resistance continues to escalate, acting as a global ticking time bomb. Numerous efforts and strategies have been employed to combat the rising levels of antibiotic resistance by targeting specific resistance mechanisms. These mechanisms include antibiotic inactivating/modifying enzymes, outer membrane porin remodelling, enhanced efflux pump action, and alteration of antibiotic target sites. Some strategies have demonstrated clinical promise, such as the utilization of beta-lactamase inhibitors as antibiotic adjuvants, as well as recent advancements in machine-based learning employing artificial intelligence to facilitate the production of novel narrow-spectrum antibiotics. However, further research into an enhanced understanding of the precise mechanisms by which antibiotic resistance occurs, specifically tailored to each bacterial species, could pave the way for exploring narrow-spectrum targeted therapies. This review aims to introduce the key features of Gram-negative bacteria and their current treatment approaches, summarizing the major antibiotic resistance mechanisms with a focus on Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Additionally, potential directions for alternative therapies will be discussed, along with their relative modes of action, providing a future perspective and insight into the discipline of antimicrobial resistance.
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DOI：
10.1093/jac/dkab352
发表时间：
2021-11-22
期刊：
The Journal of antimicrobial chemotherapy
影响因子：
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作者：
Bassetti M;Garau J
通讯作者：
Garau J
影响因子：
2.6
作者：
Al-Tamimi, Mohammad;Abu-Raideh, Jumana;Saleh, Saiel
通讯作者：
Saleh, Saiel
大肠杆菌的抗菌药物耐药性及其对动物健康的危害
影响因子：
1.7
作者：
通讯作者：
--
影响因子：
5.6
作者：
Amaral L;Martins A;Spengler G;Molnar J
通讯作者：
Molnar J
影响因子：
4.9
作者：
Almaghrabi, Reem;Clancy, Cornelius J.;Nguyen, M. Hong
通讯作者：
Nguyen, M. Hong