Veith P D, Glew M D, Gorasia D G, Cascales E, Reynolds E C
Oral Health CRC, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Victoria, Australia.
Laboratoire d'Ingénierie des Syst èmes Macromol éculaires (LISM), Institut de Microbiologie, Bioénergies and Biotechnologie (IM2B), Aix-Marseille Université, Centre National de la Recherche Scientifique (CNRS), UMR7255, Marseille Cedex, France.
J Dent Res. 2022 Apr;101(4):374-383. doi: 10.1177/00220345211051599. Epub 2021 Dec 10.
, and species found in severe periodontitis use the Type IX Secretion System (T9SS) to load their outer membrane surface with an array of virulence factors. These virulence factors are then released on outer membrane vesicles (OMVs), which penetrate the host to dysregulate the immune response to establish a positive feedback loop of chronic, inflammatory destruction of the tooth's supporting tissues. In this review, we present the latest information on the molecular architecture of the T9SS and provide mechanistic insight into its role in secretion and attachment of cargo proteins to produce a virulence coat on cells and OMVs. The recent molecular structures of the T9SS motor comprising PorL and PorM as well as the secretion pore Sov, together with advances in the overall interactome, have provided insight into the possible mechanisms of secretion. We propose the presence of PorL/M motors arranged in a circle at the inner membrane with bent periplasmic rotors interacting with the PorN protein. At the outer membrane, we envisage a slide carousel model where the PorN protein is driven around a circular track composed of PorK. Cargo proteins are transported by PorN to PorW and the Sov translocon just as slides are rotated to the projection window. Secreted proteins are proposed to then be shuttled along highways consisting of the PorV shuttle protein to an array of attachment complexes distributed around the cell. The cell surface attachment of cargo is a hallmark of the T9SS, and in and , this attachment is achieved via covalent bonding to a linking sugar synthesized by the Wbp/Vim pathway. The cell-surface attached cargo are enriched on OMVs, which are then released from the cell.
在重度牙周炎中发现的[具体物种]利用IX型分泌系统（T9SS）在其外膜表面装载一系列毒力因子。这些毒力因子随后在外膜囊泡（OMV）上释放，OMV穿透宿主以失调免疫反应，从而建立对牙齿支持组织的慢性炎症破坏的正反馈回路。在本综述中，我们展示了关于T9SS分子结构的最新信息，并提供了关于其在货物蛋白分泌和附着以在细胞和OMV上产生毒力涂层方面作用的机制性见解。最近由PorL和PorM以及分泌孔Sov组成的T9SS马达的分子结构，连同整体相互作用组学的进展，为分泌的可能机制提供了见解。我们提出在内膜上存在呈环状排列的PorL/M马达，弯曲的周质转子与PorN蛋白相互作用。在外膜处，我们设想一个滑动转盘模型，其中PorN蛋白围绕由PorK组成的圆形轨道驱动。货物蛋白由PorN运输到PorW和Sov转运体，就像幻灯片旋转到投影窗口一样。然后，分泌的蛋白质沿着由PorV穿梭蛋白组成的高速公路穿梭到分布在细胞周围的一系列附着复合物中。货物在细胞表面的附着是T9SS的一个标志，在[具体物种1]和[具体物种2]中，这种附着是通过与由Wbp/Vim途径合成的连接糖共价结合来实现的。细胞表面附着的货物在OMV上富集，然后从细胞中释放出来。
