Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
Department of Veterinary Sciences, University of Kentucky College of Agriculture, Lexington, Kentucky, USA.
Infect Immun. 2023 Jul 18;91(7):e0043622. doi: 10.1128/iai.00436-22. Epub 2023 Jun 20.
The versatile type IV secretion system (T4SS) nanomachine plays a pivotal role in bacterial pathogenesis and the propagation of antibiotic resistance determinants throughout microbial populations. In addition to paradigmatic DNA conjugation machineries, diverse T4SSs enable the delivery of multifarious effector proteins to target prokaryotic and eukaryotic cells, mediate DNA export and uptake from the extracellular milieu, and in rare examples, facilitate transkingdom DNA translocation. Recent advances have identified new mechanisms underlying unilateral nucleic acid transport through the T4SS apparatus, highlighting both functional plasticity and evolutionary adaptations that enable novel capabilities. In this review, we describe the molecular mechanisms underscoring DNA translocation through diverse T4SS machineries, emphasizing the architectural features that implement DNA exchange across the bacterial membrane and license transverse DNA release across kingdom boundaries. We further detail how recent studies have addressed outstanding questions surrounding the mechanisms by which nanomachine architectures and substrate recruitment strategies contribute to T4SS functional diversity.
多功能型 IV 型分泌系统 (T4SS) 纳米机器在细菌发病机制和抗生素耐药决定因素在微生物群体中的传播中起着关键作用。除了典范的 DNA 接合机制外，各种 T4SS 还能够将多种效应蛋白递送至靶原核和真核细胞，介导 DNA 从细胞外环境的输出和摄取，并在极少数情况下促进跨界 DNA 易位。最近的研究确定了通过 T4SS 装置进行单向核酸运输的新机制，突出了功能可塑性和进化适应，使新的能力成为可能。在这篇综述中，我们描述了支撑通过不同 T4SS 机制进行 DNA 易位的分子机制，强调了实现跨细菌膜进行 DNA 交换并授权跨界释放横向 DNA 的结构特征。我们进一步详细介绍了最近的研究如何解决围绕纳米机器结构和底物募集策略如何有助于 T4SS 功能多样性的机制的悬而未决的问题。
