Loss of DNA-membrane interactions and cessation of DNA synthesis in myeloperoxidase-treated Escherichia coli.
Loss of DNA-membrane interactions and cessation of DNA synthesis in myeloperoxidase-treated Escherichia coli.
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髓过氧化物酶处理的大肠杆菌中 DNA 与膜相互作用的丧失和 DNA 合成的停止。
DOI：
10.1073/pnas.87.24.10048
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发表时间：
1990
影响因子：
11.1
通讯作者：
VanDevanter,DR
中科院分区：
文献类型：
--
作者：
Rosen,H;Orman,J;Rakita,RM;Michel,BR;VanDevanter,DR
中性粒细胞和单核细胞采用多种抗菌效应系统来支持其宿主防御功能。大多数这些系统的作用机制还不完全清楚。本报告表明，由嗜中性粒细胞衍生的抗微生物系统，髓过氧化物酶，酶促产生的过氧化氢，和氯离子组成的杀微生物活性，是伴随着迅速停止在大肠杆菌中的DNA合成，确定显着减少掺入[3 H]胸苷到三氯乙酸沉淀材料。同时，髓过氧化物酶系统介导了E.大肠杆菌膜结合含有E. coli染色体复制起点（oriC）。oriC与E.大肠杆菌细胞膜是染色体DNA有序复制的基本元件。可比较的早期变化，DNA合成和DNA-膜相互作用，没有观察到替代氧化剂或杀虫剂介导的杀微生物系统。提出髓过氧化物酶系统产生的氧化剂修饰E.大肠杆菌膜的oriC结合明显受损。因此，染色体DNA复制受损，生物体不能再复制。
Neutrophils and monocytes employ a diverse array of antimicrobial effector systems to support their host defense functions. The mechanisms of action of most of these systems are incompletely understood. The present report indicates that microbicidal activity by a neutrophil-derived antimicrobial system, consisting of myeloperoxidase, enzymatically generated hydrogen peroxide, and chloride ion, is accompanied by prompt cessation of DNA synthesis in Escherichia coli, as determined by markedly reduced incorporation of [3H]thymidine into trichloracetic acid-precipitable material. Simultaneously, the myeloperoxidase system mediates a decline in the ability of E. coli membranes to bind hemimethylated DNA sequences containing the E. coli chromosomal origin of replication (oriC). Binding of oriC to the E. coli membrane is an essential element of orderly chromosomal DNA replication. Comparable early changes in DNA synthesis and DNA-membrane interactions were not observed with alternative oxidant or antibiotic-mediated microbicidal systems. It is proposed that oxidants generated by the myeloperoxidase system modify the E. coli membrane in such a fashion that oriC binding is markedly impaired. As a consequence chromosomal DNA replication is impaired and organisms can no longer replicate.