Phenotypic heterogeneity in bacteria: the rise of antibiotic persistence, clinical implications, and therapeutic opportunities

IF 2.3 3区 生物学 Q3 MICROBIOLOGY
Srimayee Pani, Saswat S. Mohapatra
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引用次数: 0

Abstract

The rising incidence of antimicrobial resistance (AMR) and the diminishing antibiotics discovery pipeline have created an unprecedented scenario where minor infections could become untreatable. AMR phenomenon is genetically encoded, and various genetic determinants have been implicated in their emergence and spread. Nevertheless, several non-genetic phenomena are also involved in antibiotic treatment failure which requires a systematic investigation. It has been observed that in an isogenic population of bacteria, not all cells behave or respond the same way to an antibiotic, because of the inherent heterogeneity among them. This heterogeneity is not always heritable but rather phenotypic. Three distinct types of phenotypic heterogeneity, namely tolerance, persistence, and heteroresistance have been observed in bacteria having significant clinical implications influencing the treatment outcome. While tolerance is when a population can survive high doses of antibiotics without changing the minimum inhibitory concentration (MIC) of the drug, persistence occurs in a subpopulation of bacteria that can survive exposure to high antibiotic doses. In contrast, when a subpopulation shows a very high MIC in comparison to the rest of the population, the phenomenon is called heteroresistance. In this article, we have highlighted bacterial persistence with a focus on their emergence and the underlying molecular mechanisms. Moreover, we have tried to associate the genome-wide methylation status with that of the heterogeneity at a single-cell level that may explain the role of epigenetic mechanisms in the development of persistence.

细菌的表型异质性:抗生素持久性的上升、临床影响和治疗机会。
抗菌药耐药性(AMR)发病率的不断上升和抗生素研发渠道的不断减少,造成了一种前所未有的局面,即轻微感染可能变得无法治疗。AMR 现象是基因编码的,其出现和传播与各种基因决定因素有关。然而,抗生素治疗失败还与一些非遗传现象有关,需要进行系统研究。据观察,在一个同源细菌群体中,并非所有细胞对抗生素的行为或反应都相同,因为它们之间存在固有的异质性。这种异质性并不总是遗传性的,而是表型性的。在细菌中已经观察到三种不同类型的表型异质性,即耐受性、持久性和异抗性,它们对治疗结果有着重要的临床影响。耐受性是指在不改变药物最低抑菌浓度(MIC)的情况下,一个群体能在高剂量抗生素中存活下来,而持久性则发生在能在高剂量抗生素中存活下来的细菌亚群体中。与此相反,当一个亚群的最低抑菌浓度与其他群体相比非常高时,这种现象被称为异抗性。在这篇文章中,我们强调了细菌的持久性,重点是它们的出现及其潜在的分子机制。此外,我们还试图将全基因组甲基化状态与单细胞水平的异质性联系起来,以解释表观遗传机制在持久性发展中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Archives of Microbiology
Archives of Microbiology 生物-微生物学
CiteScore
4.90
自引率
3.60%
发文量
601
审稿时长
3 months
期刊介绍: Research papers must make a significant and original contribution to microbiology and be of interest to a broad readership. The results of any experimental approach that meets these objectives are welcome, particularly biochemical, molecular genetic, physiological, and/or physical investigations into microbial cells and their interactions with their environments, including their eukaryotic hosts. Mini-reviews in areas of special topical interest and papers on medical microbiology, ecology and systematics, including description of novel taxa, are also published. Theoretical papers and those that report on the analysis or ''mining'' of data are acceptable in principle if new information, interpretations, or hypotheses emerge.
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