细菌对抗菌肽的耐受机制

Mechanisms of antimicrobial peptide resistance

抗菌肽广谱、高特异、高生物活性等特点决定其具极大的临床应用潜力,然而抗菌肽的耐受是其药物开发必须重视和亟待克服的问题。从生物学的观点看,部分细菌可以产生抗菌肽,其必定存在逃避自身抗菌肽作用的机制;从进化的观点看,宿主和病原体之间是相互抑制、相互逃避、相互适应的关系,细菌在漫长的进化中会形成应对抗菌肽的特殊机制。抗菌肽对细菌存在多种作用机制,其核心是依赖于与细胞膜相互作用或进入细胞,进而改变膜完整性或干扰胞内生理生化反应导致细菌死亡;而细菌通过减弱抗菌肽结合、降低抗菌肽有效浓度等方式产生对抗菌肽的耐受。这些耐受机制也为抗菌肽类药物开发提供重要的启示。

Antimicrobial peptides （AMPs） are considered as potential anti-infective agents because of their broad- spectrum, highly effective and specific activities. Resistance to AMPs is an obstacle that must be paid more attention and overcome. From biological viewpoint, some bacteria can produce AMPs, so they should own certain strategy to tolerate their own AMPs. Moreover, in evolutionary perspective, host-pathogen interaction is the result of mutual struggle, evasion and adaptation over millions of years, so microbes might develop some strategies against AMPs. There are a variety of mechanisms that AMPs act on bacteria, among which the most important mechanisms are that the AMPs interact with cell membrane or enter into bacteria, resulting in the death of bacteria by altering the integrity of the membrane or disturbing intracellular physiological and biochemical reactions. On the contrary, bacteria can tolerate AMPs by weakening the binding of AMPs and decreasing the effective concentration of AMPs. These resistance mechanisms provide us inspiration for the drug development of AMPs.