Uddin Md Rasel, Saifullah Saifullah
Department of Genetic Engineering and Biotechnology, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore, 7408, Bangladesh.
Arch Microbiol. 2025 Sep 19;207(11):269. doi: 10.1007/s00203-025-04467-0.
Simple early lifeforms with relatively small genomes were evolved with certain genetic circuitry to better their stress-response mechanism which significantly enhances their survival during stress, hypothetically. In this review, we conducted a comprehensive investigation to identify survival-focused genetic circuitry in microorganisms, focusing on type II toxin-antitoxin (TA) systems, particularly sought after due to their ubiquitousness in nature, composed of two functionally coordinated genes: one that transiently inhibits reproduction during stress and another that represses this inhibition under normal conditions, while simultaneously promoting DNA repair under stress. Our comprehensive analysis of 22 type II TA systems reveals diverse roles, including dormancy induction, biofilm formation, pathogenicity and DNA repair. While canonical modules such as HigAB and RelBE are well-characterized, others like ParDE, Kid-Kis, and YafO-YafN remain understudied in the context of dormancy or biofilm involvement. Additionally, systems such as DarT-DarG, YafQ-DinJ and CcdB-CcdA have been implicated in DNA repair pathways, suggesting broader functional repertoires beyond growth inhibition. Phylogenetic analyses further reveal that TA systems such as VapC-VapB and MazF-MazE are widely distributed among bacteria, archaea, and cyanobacteria, including lineages thriving in extreme environments like deep-sea hydrothermal vents, which are considered potential sites for the emergence of early life. The presence of TA loci in ancient microorganisms like Methanocaldococcus jannaschii and Microcystis aeruginosa hints at their ancient origin and possible role in microbial survival on early Earth. This review synthesizes current knowledge on type II TA systems as stress-responsive survival circuits and highlights their significance in microbial ecology, evolution, and adaptation.
具有相对较小基因组的简单早期生命形式通过特定的遗传电路进化，以改善其应激反应机制，假设这能显著提高它们在应激期间的存活率。在本综述中，我们进行了全面调查，以确定微生物中以生存为重点的遗传电路，重点关注II型毒素-抗毒素（TA）系统，因其在自然界中无处不在而备受关注，该系统由两个功能协调的基因组成：一个在应激期间短暂抑制繁殖，另一个在正常条件下抑制这种抑制，同时在应激时促进DNA修复。我们对22个II型TA系统的综合分析揭示了其多样的作用，包括诱导休眠、形成生物膜、致病性和DNA修复。虽然像HigAB和RelBE这样的典型模块已得到充分研究，但其他如ParDE、Kid-Kis和YafO-YafN在休眠或生物膜参与方面仍未得到充分研究。此外，DarT-DarG、YafQ-DinJ和CcdB-CcdA等系统已被证明参与DNA修复途径，这表明其功能范围比生长抑制更广泛。系统发育分析进一步表明，VapC-VapB和MazF-MazE等TA系统广泛分布于细菌、古菌和蓝细菌中，包括在深海热液喷口等极端环境中繁衍生息的谱系，这些环境被认为是早期生命出现的潜在地点。在詹氏甲烷球菌和铜绿微囊藻等古老微生物中存在TA基因座，这暗示了它们的古老起源以及在早期地球微生物生存中的可能作用。本综述综合了关于II型TA系统作为应激反应生存电路的当前知识，并强调了它们在微生物生态学、进化和适应中的重要性。
