Phenotypic heterogeneity in persisters: a novel 'hunker' theory of persistence.
Phenotypic heterogeneity in persisters: a novel 'hunker' theory of persistence.
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持久性的表型异质性：持久性的新“亨克”理论。
DOI：
10.1093/femsre/fuab042
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发表时间：
2022-01-18
影响因子：
11.3
通讯作者：
McFadden J
中科院分区：
文献类型：
--
作者：
Urbaniec J;Xu Y;Hu Y;Hingley-Wilson S;McFadden J
自70多年前发现以来，耐受性一直与治疗失败有关，了解这一关键的抗生素耐药亚群的形成、性质和生存对于提高治疗成功和对抗抗菌素耐药性(AMR)的威胁至关重要。“持久力”一词经常与其他术语互换使用，如耐受性或休眠。在这篇综述中，我们将重点放在抗生素持久性上，我们广泛地将其定义为具有暴露于一种或多种抗生素的非遗传性的细菌细胞亚群的特征；并且作为具有这种特征的细胞而持久存在。我们讨论了参与宿存细胞形成的新的分子机制，以及有助于提高体内抗生素持久性的环境因素，重点介绍了单细胞研究的最新进展。我们还旨在提供一个全面的持久性模型，即基于细菌种群内在异质性的“驼背”理论，以及有助于持久亚种群抗生素生存的无数“蹲下”机制。最后，我们讨论了抗生素的持久性作为AMR的“垫脚石”，并强调迫切需要开发有效的抗持续性治疗方案来治疗这一具有高度临床相关性的细菌亚群。本文讨论了抗生素持久性领域的最新进展，旨在基于细菌生长和代谢的内在异质性，提供一种新的、全面的宿存细胞形成理论。
Persistence has been linked to treatment failure since its discovery over 70 years ago and understanding formation, nature and survival of this key antibiotic refractory subpopulation is crucial to enhancing treatment success and combatting the threat of antimicrobial resistance (AMR). The term ‘persistence’ is often used interchangeably with other terms such as tolerance or dormancy. In this review we focus on ‘antibiotic persistence’ which we broadly define as a feature of a subpopulation of bacterial cells that possesses the non-heritable character of surviving exposure to one or more antibiotics; and persisters as cells that possess this characteristic. We discuss novel molecular mechanisms involved in persister cell formation, as well as environmental factors which can contribute to increased antibiotic persistence in vivo, highlighting recent developments advanced by single-cell studies. We also aim to provide a comprehensive model of persistence, the ‘hunker’ theory which is grounded in intrinsic heterogeneity of bacterial populations and a myriad of ‘hunkering down’ mechanisms which can contribute to antibiotic survival of the persister subpopulation. Finally, we discuss antibiotic persistence as a ‘stepping-stone’ to AMR and stress the urgent need to develop effective anti-persister treatment regimes to treat this highly clinically relevant bacterial sub-population. This review discusses recent developments in the field of antibiotic persistence, and aims to provide a novel, comprehensive ‘hunker’ theory of persister cell formation based on intrinsic heterogeneity of bacterial growth and metabolism.
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影响因子：
4.5
作者：
Bernier SP;Lebeaux D;DeFrancesco AS;Valomon A;Soubigou G;Coppée JY;Ghigo JM;Beloin C
通讯作者：
Beloin C
影响因子：
30.3
作者：
Cohen NR;Lobritz MA;Collins JJ
通讯作者：
Collins JJ
DOI：
10.1073/pnas.1631248100
发表时间：
2003-08-19
影响因子：
11.1
作者：
Dahl, JL;Kraus, CN;Barry, CE
通讯作者：
Barry, CE
影响因子：
3.7
作者：
Barraud N;Buson A;Jarolimek W;Rice SA
通讯作者：
Rice SA
影响因子：
5.2
作者：
de Steenwinkel, Jurriaan E. M.;de Knegt, Gerjo J.;Bakker-Woudenberg, Irma A. J. M.
通讯作者：
Bakker-Woudenberg, Irma A. J. M.