细菌抗菌肽耐药机制研究进展

Advances in studying bacterial resistance to antimicrobial peptides

摘要:

细菌对传统抗生素的耐药程度十分严重，寻找克服耐药性的新型抗菌药物已成为当务之急。抗菌肽（antimicrobial peptides，AMPs）是当下较有前景的抗菌药物之一。虽然通常认为，AMPs优先攻击细胞膜的特点使其不会引起广泛的耐药性，但其对特定靶标的识别能力仍为基因突变和细菌耐药性的产生提供了可能。此外，一些细菌还显示出了抵御宿主AMPs的杀伤作用并与宿主细胞共存的能力，相应的细菌防御机制也使其对治疗性AMPs产生抗性，这种交叉抗性近年来也备受关注。这些耐药现象的发现均对AMPs的开发提出了新挑战。本综述就细菌对AMPs耐药的分子机制进行了研究进展的总结，并且对治疗性AMPs与宿主防御肽交叉抗性的相关机制研究进行了归纳，以期寻求新的对抗耐药性的策略。

关键词:交叉耐药性;宿主防御肽;细胞膜;荚膜;磷壁酸;脂多糖

Abstract:

Bacteria have developed severe resistance to traditional antibiotics, demanding novel antimicrobial agents to overcome resistance. Antimicrobial peptides are promising novel antimicrobial agents. Owing to preferential attack on the cell membrane, antimicrobial peptides will not lead to widespread resistance, although their recognition of specific targets might cause genetic mutations and resistance of the targets. Additionally, some bacteria can overcome endogenous antimicrobial peptides and survive with the host cells. The corresponding defense mechanisms of bacteria also bring cross-resistance to therapeutic antimicrobial peptides. The resistance mentioned above poses a challenge to the development of antimicrobial peptides. In this review, we summarize the research progress in studying the mechanisms of antimicrobial peptides resistance, to provide the reference for developing strategies to fight bacterial resistance.

Key words:cross-resistance;host defense peptide;cell membrane;capsule;teichoic acid;lipopolysaccharide