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Type VII secretion systems: structure, functions and transport models. ​

文献信息 ​

DOI10.1038/s41579-021-00560-5
PMID34040228
期刊Nature reviews. Microbiology
影响因子103.3
JCR 分区Q1
发表年份2021
被引次数47
关键词第七型分泌系统, 分泌效应蛋白, 分子生物学
文献类型Journal Article, Research Support, Non-U.S. Gov't, Review
ISSN1740-1526
页码567-584
期号19(9)
作者Angel Rivera-Calzada, Nikolaos Famelis, Oscar Llorca, Sebastian Geibel

一句话小结 ​

第VII型分泌系统（T7SS）在结核分枝杆菌中起着关键作用，帮助其分泌效应蛋白并逃避宿主免疫，导致全球每年140万人死亡。该研究综述了T7SS的结构特征及其分子生物学进展，为开发针对结核病的新治疗策略提供了重要基础。

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第七型分泌系统 · 分泌效应蛋白 · 分子生物学

摘要 ​

第VII型分泌系统（T7SS）在非致病性分枝杆菌和致病性分枝杆菌（如肺结核的主要病原体——结核分枝杆菌）中扮演着关键角色，负责分泌效应蛋白。导致结核病的分枝杆菌每年仍造成140万人死亡，它们依赖于同源的T7SS在宿主内生存并有效地逃避宿主的免疫反应。尽管目前仍不清楚T7SS的效应蛋白如何穿越双膜的分枝杆菌细胞膜，但最近在这些分泌系统的结构特征方面取得的进展揭示了质膜中保守成分复杂的相互作用网络。这些结构信息，加上最近在分枝杆菌T7SS的分子生物学和调控方面的进展，以及对其分泌效应蛋白理解的深化，为我们揭示了T7SS机制的内部运作。本综述重点突出这些研究的意义及其衍生的运输模型，为针对致命的人类病原体结核分枝杆菌提供了新的策略。

英文摘要 ​

Type VII secretion systems (T7SSs) have a key role in the secretion of effector proteins in non-pathogenic mycobacteria and pathogenic mycobacteria such as Mycobacterium tuberculosis, the main causative agent of tuberculosis. Tuberculosis-causing mycobacteria, still accounting for 1.4 million deaths annually, rely on paralogous T7SSs to survive in the host and efficiently evade its immune response. Although it is still unknown how effector proteins of T7SSs cross the outer membrane of the diderm mycobacterial cell envelope, recent advances in the structural characterization of these secretion systems have revealed the intricate network of interactions of conserved components in the plasma membrane. This structural information, added to recent advances in the molecular biology and regulation of mycobacterial T7SSs as well as progress in our understanding of their secreted effector proteins, is shedding light on the inner working of the T7SS machinery. In this Review, we highlight the implications of these studies and the derived transport models, which provide new scenarios for targeting the deathly human pathogen M. tuberculosis.

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主要研究问题 ​

  1. Type VII分泌系统在不同种类的分枝杆菌中是否表现出结构和功能上的差异？
  2. 近年来对T7SS的研究进展对抗击结核病的治疗策略有何影响？
  3. T7SS的效应蛋白如何在宿主免疫反应中发挥作用，是否有特定的机制？
  4. 在分枝杆菌的外膜穿透机制上，是否有新的研究方向或假说正在被探索？
  5. 针对T7SS的靶向治疗是否有可能引发耐药性的问题，相关研究有哪些？

核心洞察 ​

1. 研究背景和目的 ​

本研究聚焦于第七型分泌系统（T7SS）的结构、功能及其运输模型，特别是在非致病性和致病性分枝杆菌（如结核分枝杆菌）中的作用。结核分枝杆菌是导致结核病的主要病原体，每年造成约140万人死亡。研究的目的是深入理解T7SS在分枝杆菌生存和逃逸宿主免疫反应中的机制，为开发针对结核病的新治疗策略提供理论基础。

2. 主要方法和发现 ​

研究通过先进的结构生物学技术，对T7SS的组成部分进行了详细的结构表征，揭示了其在质膜中的复杂相互作用网络。此外，结合分子生物学和调控研究，分析了T7SS的功能及其分泌的效应蛋白。这些研究成果显示，尽管T7SS效应蛋白如何穿越分枝杆菌的外膜仍不清晰，但对其运输机制的理解正在逐步深入。

3. 核心结论 ​

研究表明，T7SS在结核分枝杆菌的生存和致病性中扮演了至关重要的角色。通过解析T7SS的结构和功能，研究提供了有关其效应蛋白分泌机制的新见解，并提出了新的运输模型。这些发现不仅帮助理解分枝杆菌如何逃避宿主的免疫反应，也为未来的药物开发提供了新的靶点。

4. 研究意义和影响 ​

本研究揭示了T7SS在分枝杆菌致病性中的重要性，具有深远的临床意义。了解T7SS的结构和功能，为开发针对结核病的新型抗生素或疫苗提供了新的思路。随着对T7SS及其效应蛋白的认识不断加深，有望推动结核病的治疗和预防策略的创新，最终降低全球结核病的发病率和死亡率。此外，这项研究为其他致病性细菌的分泌系统提供了借鉴，可能对更广泛的感染性疾病研究产生积极的影响。

参考文献 ​

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  8. Bacterial nanomachines: the flagellum and type III injectisome. - Marc Erhardt;Keiichi Namba;Kelly T Hughes - Cold Spring Harbor perspectives in biology (2010)
  9. A view to a kill: the bacterial type VI secretion system. - Brian T Ho;Tao G Dong;John J Mekalanos - Cell host & microbe (2014)
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引用本文的文献 ​

  1. A Small Protein but with Diverse Roles: A Review of EsxA in Mycobacterium-Host Interaction. - Yanqing Bao;Lin Wang;Jianjun Sun - Cells (2021)
  2. Secretion Systems in Gram-Negative Bacterial Fish Pathogens. - Sophanit Mekasha;Dirk Linke - Frontiers in microbiology (2021)
  3. A Comparative Analysis of Weizmannia coagulans Genomes Unravels the Genetic Potential for Biotechnological Applications. - Martina Aulitto;Laura Martinez-Alvarez;Gabriella Fiorentino;Danila Limauro;Xu Peng;Patrizia Contursi - International journal of molecular sciences (2022)
  4. Peptidomimetics as Potential Anti-Virulence Drugs Against Resistant Bacterial Pathogens. - Osmel Fleitas Martínez;Harry Morales Duque;Octávio Luiz Franco - Frontiers in microbiology (2022)
  5. Design Principles of the Rotary Type 9 Secretion System. - Abhishek Trivedi;Jitendrapuri Gosai;Daisuke Nakane;Abhishek Shrivastava - Frontiers in microbiology (2022)
  6. Comparative Genomic Analysis of Type VII Secretion System in Streptococcus agalactiae Indicates Its Possible Sequence Type-Dependent Diversity. - Kaixin Zhou;Lianyan Xie;Xiaogang Xu;Jingyong Sun - Frontiers in cellular and infection microbiology (2022)
  7. Proteo-genetic analysis reveals clear hierarchy of ESX-1 secretion in Mycobacterium marinum. - Rachel M Cronin;Micah J Ferrell;Clare W Cahir;Matthew M Champion;Patricia A Champion - Proceedings of the National Academy of Sciences of the United States of America (2022)
  8. Are Virulence and Antibiotic Resistance Genes Linked? A Comprehensive Analysis of Bacterial Chromosomes and Plasmids. - Helena Darmancier;Célia P F Domingues;João S Rebelo;Ana Amaro;Francisco Dionísio;Joël Pothier;Octávio Serra;Teresa Nogueira - Antibiotics (Basel, Switzerland) (2022)
  9. Bacterial secretion systems: Networks of pathogenic regulation and adaptation in mycobacteria and beyond. - Kathleen R Nicholson;Patricia A Champion - PLoS pathogens (2022)
  10. Immune evasion and provocation by Mycobacterium tuberculosis. - Pallavi Chandra;Steven J Grigsby;Jennifer A Philips - Nature reviews. Microbiology (2022)

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