青霉素结合蛋白及其介导细菌耐药的研究进展

Research progress in penicillin binding proteins and their mediated bacterial resistance

青霉素结合蛋白(PBPs)是一类广泛存在于细菌细胞膜表面的膜蛋白,是β-内酰胺类抗生素的主要作用靶位。在细菌合成细胞壁肽聚糖的过程中,PBPs主要发挥糖基转移酶、肽基转移酶和D-丙氨酰-D-丙氨酸羧肽酶(D,D-羧肽酶)活性,是细菌生长繁殖中不可或缺的酶。不同种类细菌所含PBPs各不相同,其结构的改变、数量的增多、与抗生素亲和力的下降以及产生新的青霉素结合蛋白是直接导致细菌对β-内酰胺类抗生素产生耐药性的重要原因。随着各类抗菌药物在临床上的广泛应用,细菌对抗菌药物的耐药问题日趋严重,其耐药水平也越来越高。因此,近年来全球围绕PBPs开展的研究工作越来越多。本文对PBPs的分类、结构和功能、与细菌耐药性的关系及检测方法的最新研究进展进行综述,并对未来可能的研究方向进行展望。

Penicillin binding proteins（PBPs） are a class of membrane proteins that are widely present on the surface of bacteria. They are the main target of β-lactam antibiotics. In the process of the bacterial cell wall peptidoglycan synthesis, PBPs play key roles of glycosyl transferase, peptidyl transferase and D-alanyl-D-alanine carboxypeptidase and thus are indispensable for bacterial growth. Different bacteria contain various PBPs. Changes of protein structure, increase of quantity, decrease of susceptibility to antibiotics and production of new PBPs are important reasons resulting in drug-resistance to β-lactam antibiotics. With wide use of different antibacterial agents, the problem of bacterial resistance is becoming increasingly serious. Therefore, research on PBPs has been carried out in recent years around the world. In this paper, the classification, structure and function of PBPs, their relationship with bacterial drug-resistance and detection methods are summarized. This paper also indicates future research directions.