Rakita R M, Rosen H
Department of Medicine, University of Washington, Seattle 98195.
J Clin Invest. 1991 Sep;88(3):750-4. doi: 10.1172/JCI115372.
Myeloperoxidase (MPO), H2O2, and chloride comprise a potent antimicrobial system believed to contribute to the antimicrobial functions of neutrophils and monocytes. The mechanisms of microbicidal action are complex and not fully defined. This report describes the MPO-mediated inactivation, in Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, of a class of cytoplasmic membrane enzymes (penicillin-binding proteins, PBPs) found in all eubacteria, that covalently bind beta-lactam antibiotics to their active sites with loss of enzymatic activity. Inactivation of "essential" PBPs, including PBP1-PBP3 of E. coli, leads to unbalanced bacterial growth and cell death. MPO treatment of bacteria was associated with loss of penicillin binding by PBPs, strongly suggesting PBP inactivation. In E. coli, PBP inactivation was most rapid with PBP3, where the rate of decline in binding activity approximated but did not equal loss of viability. Changes in E. coli morphology (elongation), observed just before bacteriolysis, were consistent with early predominant inactivation of PBP3. We conclude that inactivation of essential PBPs is sufficient to account for an important fraction of MPO-mediated bacterial action. This feature of MPO action interestingly recapitulates an antibacterial strategy evolved by beta-lactam-producing molds that must compete with bacteria for limited ecologic niches.
髓过氧化物酶（MPO）、过氧化氢（H₂O₂）和氯离子构成了一个强大的抗菌系统，据信该系统有助于中性粒细胞和单核细胞发挥抗菌功能。其杀菌作用机制复杂，尚未完全明确。本报告描述了MPO介导的对大肠杆菌、金黄色葡萄球菌和铜绿假单胞菌中一类细胞质膜酶（青霉素结合蛋白，PBPs）的失活作用，这类酶存在于所有真细菌中，能将β-内酰胺抗生素共价结合到其活性位点，导致酶活性丧失。包括大肠杆菌的PBP1 - PBP3在内的“必需”PBPs失活会导致细菌生长失衡和细胞死亡。用MPO处理细菌与PBPs的青霉素结合能力丧失有关，强烈提示PBP失活。在大肠杆菌中，PBP3的失活速度最快，其结合活性下降速率接近但不等于生存能力的丧失。在细菌溶解前观察到的大肠杆菌形态变化（伸长）与PBP3早期的主要失活一致。我们得出结论，必需PBPs的失活足以解释MPO介导的细菌作用的很大一部分。MPO作用的这一特性有趣地重现了产生β-内酰胺的霉菌所进化出的一种抗菌策略，这些霉菌必须与细菌争夺有限的生态位。
