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Bacterial fatty acid metabolism in modern antibiotic discovery.细菌脂肪酸代谢与现代抗生素发现。
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Novel Targets of Antimicrobial Therapies.新型抗菌治疗靶点。
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Regulating effect of β-ketoacyl synthase domain of fatty acid synthase on fatty acyl chain length in de novo fatty acid synthesis.脂肪酸合酶的β-酮酰基合酶结构域在从头脂肪酸合成中对脂肪酰链长度的调控作用。
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The antibiotic resistance crisis: part 1: causes and threats.抗生素耐药性危机:第一部分:成因与威胁。
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Activity of Debio1452, a FabI inhibitor with potent activity against Staphylococcus aureus and coagulase-negative Staphylococcus spp., including multidrug-resistant strains.Debio1452的活性,一种对金黄色葡萄球菌和凝固酶阴性葡萄球菌(包括多重耐药菌株)具有强效活性的FabI抑制剂。
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Antibiotics and bacterial resistance in the 21st century.21世纪的抗生素与细菌耐药性
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Evolution of acyl-ACP-thioesterases and β-ketoacyl-ACP-synthases revealed by protein-protein interactions.通过蛋白质-蛋白质相互作用揭示的酰基-ACP硫酯酶和β-酮酰基-ACP合酶的进化
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Mechanisms of self-resistance in the platensimycin- and platencin-producing Streptomyces platensis MA7327 and MA7339 strains.产生扁枝衣霉素和扁枝菌素的天蓝色链霉菌MA7327和MA7339菌株中的自身抗性机制。
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Antimicrobial resistance in Asia: current epidemiology and clinical implications.亚洲的抗菌药物耐药性:当前的流行病学及临床意义
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Advances in the research of β-ketoacyl-ACP synthase III (FabH) inhibitors.β-酮酰基-ACP 合酶 III(FabH)抑制剂的研究进展。
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抗菌药物的新靶点

Novel Targets for Antimicrobials.

作者信息

Gupta Suchita, Undale Vaishali Ravindra, Lakhadive Kedar

机构信息

Dr. D.Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra.

出版信息

Turk J Pharm Sci. 2020 Oct;17(5):565-575. doi: 10.4274/tjps.galenos.2020.90197. Epub 2020 Oct 30.

DOI:10.4274/tjps.galenos.2020.90197
PMID:33177939
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7650728/
Abstract

Antimicrobial resistance (AMR) is the phenomenon developed by microorganism on exposure to antimicrobial agents, making them unresponsive. Development of microbial confrontation is a severe rising risk to global community well-being as treatment in addition, management of such resistant microbial infections is difficult and challenging. The situation requires action across all government sectors and society. The change in the molecular target on which antimicrobial drugs act is one of the key mechanisms behind AMR. One of the approaches to battle with AMR can be exploring newer molecular targets in microbes and discovering new molecules accordingly. There are various examples of novel targets such as biomolecules involving in biosynthesis of cell wall, biosynthesis of aromatic amino acid, cell disunion, biosynthesis of fatty acid, and isoprenoid biosynthesis and tRNA synthetases. Fatty acid biosynthesis (FAB) and their enzymes among all the above is the more appealing target for the advancement of new antimicrobial agents. Number of promising inhibitors have been developed for bacterial fatty acid synthesis (FAS) and also few of them are clinically used. Some of these potential inhibitors are found to be used in development of new antibacterial as a lead compound and have been discovered from high throughput screening processes like Platencimycin and their analogue, Platencin. The review majorly encompasses bacterial FAB in type II FAS system and potential inhibitors with respective targets of novel antibacterial.

摘要

抗菌药物耐药性(AMR)是微生物在接触抗菌剂后产生的一种现象,使它们不再敏感。微生物对抗的发展对全球公共健康构成了严重且不断上升的风险,此外,治疗此类耐药微生物感染既困难又具有挑战性。这种情况需要所有政府部门和全社会采取行动。抗菌药物作用的分子靶点发生变化是AMR背后的关键机制之一。对抗AMR的方法之一是探索微生物中的新分子靶点,并据此发现新分子。有各种新靶点的例子,如参与细胞壁生物合成、芳香族氨基酸生物合成、细胞分裂、脂肪酸生物合成、类异戊二烯生物合成的生物分子以及tRNA合成酶。在上述所有靶点中,脂肪酸生物合成(FAB)及其酶是新型抗菌剂研发中更具吸引力的靶点。已经开发出了许多针对细菌脂肪酸合成(FAS)的有前景的抑制剂,其中一些已在临床上使用。这些潜在抑制剂中的一些被发现可作为先导化合物用于新型抗菌药物的研发,并且是从高通量筛选过程中发现的,如扁平霉素及其类似物扁平菌素。本综述主要涵盖II型脂肪酸合成系统中的细菌脂肪酸生物合成以及新型抗菌药物各自靶点的潜在抑制剂。