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[细菌和古细菌中非遗传性抗生素耐受性的分子机制]

[Molecular Mechanisms of Non-Inherited Antibiotic Tolerance in Bacteria and Archaea].

作者信息

Khlebodarova T M, Likhoshvai V A

机构信息

Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia.

出版信息

Mol Biol (Mosk). 2019 Jul-Aug;53(4):531-540. doi: 10.1134/S0026898419040050.

Abstract

The phenomenon of bacterial persistence, also known as non-inherited antibiotic tolerance in a part of bacterial populations, was described more than 70 years ago. This type of tolerance contributes to the chronization of infectious diseases, including tuberculosis. Currently, the emergence of persistent cells in bacterial populations is associated with the functioning of some stress-induced molecular triggers, including toxin-antitoxin systems. In the presented review, genetic and metabolic peculiarities of persistent cells are considered and the mechanisms of their occurrence are discussed. The hypothesis of the origin of persister cells based on bistability, arising due to the non-linear properties of a coupled transcription-translation system, was proposed. Within this hypothesis, the phenomenon of the bacterial persistence of modern cells is considered as a result of the genetic fixation of the phenotypic multiplicity that emerged in primitive cells in the process of neutrally coupled co-evolution (genetic drift of multiple neutrally coupled mutations). Our hypothesis explains the properties of persister cells, as well as their origin and "ineradicable" nature.

摘要

细菌持留现象,也被称为部分细菌群体中的非遗传性抗生素耐受性,早在70多年前就被描述过。这种耐受性导致了包括结核病在内的传染病的慢性化。目前,细菌群体中持留细胞的出现与一些应激诱导分子触发因素的作用有关,包括毒素-抗毒素系统。在本综述中,我们考虑了持留细胞的遗传和代谢特性,并讨论了它们的产生机制。提出了基于双稳态的持留细胞起源假说,该双稳态是由于耦合转录-翻译系统的非线性特性而产生的。在这一假说中,现代细胞的细菌持留现象被认为是原始细胞在中性耦合共同进化过程中出现的表型多样性的遗传固定结果(多个中性耦合突变的遗传漂变)。我们的假说解释了持留细胞的特性,以及它们的起源和“无法根除”的性质。

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