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Bacterial programmed cell death systems as targets for antibiotics

机译：细菌程序性细胞死亡系统作为抗生素的靶标

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摘要

Growing experimental evidence has revealed the existence of programmed cell death (PCD) systems in bacteria. Among these is the mazEF system, which is a regulable suicide module located on the chromosome of E. coli and of some other bacteria, including pathogens. Several well-known antibiotics have recently been found to cause cell death in E. coli by indirectly activating this built-in suicide module. These antibiotics belong to two groups: (i) inhibitors of transcription and/or translation; and (ii) inhibitors of folic acid metabolism resulting in thymine starvation. These data, together with the recent elucidation of the crystal structure of mazEF-directed components, hold promise for a rational chemical design of a new class of antibiotics that directly activate chromosomal suicide modules by interacting with their components. Because multi-drug resistance among bacterial pathogens is becoming more widespread, the results obtained might be useful as a basis for producing alternative drugs.
机译：越来越多的实验证据表明细菌中存在程序性细胞死亡（PCD）系统。其中之一是mazEF系统，该系统是位于大肠杆菌和某些其他细菌（包括病原体）染色体上的可调节自杀模块。最近发现了几种众所周知的抗生素，它们通过间接激活这种内置的自杀模块而导致大肠杆菌中的细胞死亡。这些抗生素分为两类：（i）转录和/或翻译抑制剂; （ii）导致胸腺嘧啶饥饿的叶酸代谢抑制剂。这些数据，以及最近对mazEF定向成分的晶体结构的阐明，为合理设计新型抗生素（通过与它们的成分相互作用直接激活染色体自杀模块）的新型抗生素提供了希望。由于细菌病原体之间的多药耐药性变得越来越普遍，因此获得的结果可能可作为生产替代药物的基础。

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