Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, Houston, TX 77030.
Microbiol Spectr. 2016 Jun;4(3). doi: 10.1128/microbiolspec.VMBF-0024-2015.
Bacterial pathogens employ type IV secretion systems (T4SSs) for various purposes to aid in survival and proliferation in eukaryotic hosts. One large T4SS subfamily, the conjugation systems, confers a selective advantage to the invading pathogen in clinical settings through dissemination of antibiotic resistance genes and virulence traits. Besides their intrinsic importance as principle contributors to the emergence of multiply drug-resistant "superbugs," detailed studies of these highly tractable systems have generated important new insights into the mode of action and architectures of paradigmatic T4SSs as a foundation for future efforts aimed at suppressing T4SS machine function. Over the past decade, extensive work on the second large T4SS subfamily, the effector translocators, has identified a myriad of mechanisms employed by pathogens to subvert, subdue, or bypass cellular processes and signaling pathways of the host cell. An overarching theme in the evolution of many effectors is that of molecular mimicry. These effectors carry domains similar to those of eukaryotic proteins and exert their effects through stealthy interdigitation of cellular pathways, often with the outcome not of inducing irreversible cell damage but rather of reversibly modulating cellular functions. This article summarizes the major developments for the actively studied pathogens with an emphasis on the structural and functional diversity of the T4SSs and the emerging common themes surrounding effector function in the human host.
细菌病原体利用 IV 型分泌系统（T4SS）来实现各种目的，以帮助其在真核宿主中生存和增殖。大型 T4SS 亚家族之一的共轭系统通过传播抗生素耐药基因和毒力特征，为入侵病原体在临床环境中提供了选择性优势。除了作为多药耐药“超级细菌”出现的主要原因之一具有内在重要性外，对这些高度可处理系统的详细研究为作用模式和典范 T4SS 的结构提供了重要的新见解，为抑制 T4SS 机器功能的未来努力奠定了基础。在过去的十年中，对第二大 T4SS 亚家族——效应物转运器的广泛研究已经确定了病原体用来颠覆、制服或绕过宿主细胞过程和信号通路的无数机制。许多效应物进化的一个主要主题是分子模拟。这些效应物携带类似于真核蛋白的结构域，并通过细胞途径的巧妙交错发挥作用，其结果通常不是诱导不可逆的细胞损伤，而是可逆地调节细胞功能。本文总结了具有活性研究的病原体的主要进展，重点介绍了 T4SS 的结构和功能多样性，以及围绕人类宿主中效应物功能的新兴共同主题。
