Martin H H, Staboulis D, Schilf W
Immun Infekt. 1981;9(3):99-105.
Bacteria contain several isofunctional, beta-lactam sensitive membrane enzymes engaged in the synthesis of cell wall peptidoglycan (peptidoglycan-DD-carboxypeptidases, -transpeptidases, -endopeptidases) as members of sets of even more numerous membrane proteins with specific, high binding-affinity for beta-lactam antibiotics (penicillin-binding proteins, PBPs). Effective inhibition of bacterial growth by beta-lactam antibiotics requires simultaneous inactivation of the essential functions of several PBPs by formation of stable enzyme-antibiotic complexes. Failure to achieve permanent inactivation of all essential targets by a given beta-lactam appears to be another cause of bacterial beta-lactam resistance, in addition to known resistance mechanisms based on action of beta-lactamases and on screening off targets from antibiotic by a penetration barrier. Different groups of beta-lactam antibiotics vary characteristically in their affinity for specific essential PBPs. Combined application of two beta-lactams which complement each other in the inactivation to essential targets is a possibility to overcome resistance of single antibiotics.
细菌含有几种功能相同、对β-内酰胺敏感的膜酶，参与细胞壁肽聚糖的合成（肽聚糖-DD-羧肽酶、转肽酶、内肽酶），它们是对β-内酰胺抗生素具有特异性高结合亲和力的更多膜蛋白集合的成员（青霉素结合蛋白，PBPs）。β-内酰胺抗生素有效抑制细菌生长需要通过形成稳定的酶-抗生素复合物同时使几种PBPs的基本功能失活。除了基于β-内酰胺酶作用和通过渗透屏障将靶点与抗生素隔离开来的已知耐药机制外，给定的β-内酰胺未能使所有基本靶点永久失活似乎是细菌对β-内酰胺耐药的另一个原因。不同组的β-内酰胺抗生素对特定基本PBPs的亲和力具有特征性差异。联合应用两种在使基本靶点失活方面相互补充的β-内酰胺是克服单一抗生素耐药性的一种可能性。
