针对金黄色葡萄球菌细胞膜的抗菌肽和小分子。

IF 8 1区 生物学 Q1 MICROBIOLOGY
Microbiology and Molecular Biology Reviews Pub Date : 2023-06-28 Epub Date: 2023-04-27 DOI:10.1128/mmbr.00037-22
Narchonai Ganesan, Biswajit Mishra, LewisOscar Felix, Eleftherios Mylonakis
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引用次数: 0

摘要

由于金黄色葡萄球菌感染的发病率高、毒力强且出现了耐药机制,因此临床治疗金黄色葡萄球菌感染是一项挑战。耐药菌株(如耐甲氧西林金黄色葡萄球菌(MRSA))对临床使用的抗菌药物产生耐受性和持久性,使耐药菌株的治疗变得更加复杂。为应对这些挑战,应探索膜干扰物,因为在针对金黄色葡萄球菌的药物研发过程中,一般不会考虑膜干扰物。细胞膜可保护金黄色葡萄球菌免受外部压力和抗菌剂的侵害,但以膜为靶点的抗菌剂可能不太可能促进细菌产生耐药性。非典型线性阳离子抗菌肽(AMPs)、高度修饰的 AMPs(如达托霉素(脂肽)、杆菌肽(环肽)和格列霉素 S(环肽))目前正在临床上使用。最近的研究表明,AMPs 和小分子可穿透金黄色葡萄球菌的细胞膜,抑制磷脂的生物合成,或阻断溶质在细胞外质和细胞外部之间的通道。除了针对细菌膜的主要作用机制(MOA)外,AMPs 和小分子还可能通过针对生物膜和下调金黄色葡萄球菌毒力基因等次要机制对细菌产生影响。在这篇综述中,我们将讨论细胞膜靶向 AMPs 和小分子的研究现状及其对金黄色葡萄球菌耐药生理形式(包括顽固细胞和生物膜)的潜在作用机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Antimicrobial Peptides and Small Molecules Targeting the Cell Membrane of Staphylococcus aureus.

Clinical management of Staphylococcus aureus infections presents a challenge due to the high incidence, considerable virulence, and emergence of drug resistance mechanisms. The treatment of drug-resistant strains, such as methicillin-resistant S. aureus (MRSA), is further complicated by the development of tolerance and persistence to antimicrobial agents in clinical use. To address these challenges, membrane disruptors, that are not generally considered during drug discovery for agents against S. aureus, should be explored. The cell membrane protects S. aureus from external stresses and antimicrobial agents, but membrane-targeting antimicrobial agents are probably less likely to promote bacterial resistance. Nontypical linear cationic antimicrobial peptides (AMPs), highly modified AMPs such as daptomycin (lipopeptide), bacitracin (cyclic peptide), and gramicidin S (cyclic peptide), are currently in clinical use. Recent studies have demonstrated that AMPs and small molecules can penetrate the cell membrane of S. aureus, inhibit phospholipid biosynthesis, or block the passage of solutes between the periplasm and the exterior of the cell. In addition to their primary mechanism of action (MOA) that targets the bacterial membrane, AMPs and small molecules may also impact bacteria through secondary mechanisms such as targeting the biofilm, and downregulating virulence genes of S. aureus. In this review, we discuss the current state of research into cell membrane-targeting AMPs and small molecules and their potential mechanisms of action against drug-resistant physiological forms of S. aureus, including persister cells and biofilms.

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来源期刊
CiteScore
18.80
自引率
0.80%
发文量
27
期刊介绍: Microbiology and Molecular Biology Reviews (MMBR), a journal that explores the significance and interrelationships of recent discoveries in various microbiology fields, publishes review articles that help both specialists and nonspecialists understand and apply the latest findings in their own research. MMBR covers a wide range of topics in microbiology, including microbial ecology, evolution, parasitology, biotechnology, and immunology. The journal caters to scientists with diverse interests in all areas of microbial science and encompasses viruses, bacteria, archaea, fungi, unicellular eukaryotes, and microbial parasites. MMBR primarily publishes authoritative and critical reviews that push the boundaries of knowledge, appealing to both specialists and generalists. The journal often includes descriptive figures and tables to enhance understanding. Indexed/Abstracted in various databases such as Agricola, BIOSIS Previews, CAB Abstracts, Cambridge Scientific Abstracts, Chemical Abstracts Service, Current Contents- Life Sciences, EMBASE, Food Science and Technology Abstracts, Illustrata, MEDLINE, Science Citation Index Expanded (Web of Science), Summon, and Scopus, among others.
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