Molecular Microbiology Lab, Department of Biotechnology, Berhampur University, Bhanja Bihar, Berhampur, Odisha, 760007, India.
Arch Microbiol. 2024 Oct 26;206(11):446. doi: 10.1007/s00203-024-04173-3.
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.
抗生素耐药性（AMR）的发病率不断上升，而抗生素的发现渠道却在不断减少，这使得轻微感染可能变得无法治疗，这种情况前所未有。AMR 现象是由基因编码的，各种遗传决定因素都与它们的出现和传播有关。然而，抗生素治疗失败还涉及到一些非遗传现象，这需要系统的研究。人们已经观察到，在细菌的同基因群体中，由于它们之间存在固有的异质性，并非所有细胞对抗生素的表现或反应都相同。这种异质性并不总是可遗传的，而是表型的。在具有重要临床意义的细菌中，已经观察到三种不同类型的表型异质性，即耐受性、持久性和异质性耐药性，它们影响着治疗结果。当一个群体能够在不改变药物最小抑菌浓度（MIC）的情况下耐受高剂量的抗生素时，就会出现耐受性；当细菌的一个亚群能够在高剂量抗生素暴露下存活时，就会出现持久性；相比之下，当一个亚群的 MIC 比群体中的其他部分高得多时，这种现象被称为异质性耐药性。本文重点介绍了细菌的持久性及其产生的分子机制，并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，这可能解释了表观遗传机制在持久性发展中的作用。
