嗜肺军团菌是引起军团菌肺炎以及庞蒂亚克热的革兰氏阴性胞内病原细菌, 嗜肺军团菌侵染宿主的主要特点是可以通过其IVB型毒力分泌系统, 向宿主细胞内分泌超过150种的底物效应蛋白。通过这些效应蛋白的作用, 嗜肺军团菌能够调整宿主细胞的胞内运输途径, 改变内外环境来伪装自己的吞噬泡, 干扰宿主的细胞周期, 抑制宿主细胞的凋亡, 从而有效逃避宿主细胞的防御功能, 创造出理想的胞内增殖环境。最后, 效应蛋白还可以帮助军团菌从宿主细胞中逃逸。目前, 嗜肺军团菌已经成为“病原菌-宿主相互作用”的重要研究模型, 其毒力分泌系统及其底物效应蛋白的功能也成为细胞微生物学的研究热点。对嗜肺军团菌分泌系统及效应蛋白的研究不仅能够帮助阐明病原细菌的致病机理, 还有助于推动对宿主免疫机制的更深层次的研究。文章主要针对嗜肺军团菌的毒力分泌系统, 尤其是IVB型分泌系统的结构和功能, 以及底物效应蛋白的研究进展进行了综述, 向读者展示出一个小小的细菌所拥有的那令人惊叹的、如此狡猾的生存策略和它精致的杀伤武器。
Legionella pneumophila is the intracellular bacterial pathogen that causes severe Legionnaires’ disease and flu-like Pontiac fever. To accomplish successful aggression against hosts, L. pneumophila secrets more than 150 kinds of substrate effector proteins into host cells via its Type IVB secretion system. With the multiple fuctions of effectors, L. pneumophila evades effectively the defense systems of hosts, converts or adjusts intracellular vesicular transport of hosts, modifies or disguises its Legionella containing vacuole (LCV), modulates the cell cycle program and inhibits the apoptosis of host cells, and finally gains the confortable intracellular replicative niche. Effectors can also help L. pneumophila escape from hosts cells after completing the proliferation.. L. pneumophila has became the distinct model for pathogen-host interaction research, and its secretion systems as well as the substrate effectors are attracting more and more attentions. Researching on T4BSS and effectors could not only help investigate the pathogenesis of intracellular bacterial pathogens, but also promote the comprehension about innate immune responses of hosts. This article reviews the progresses of L. pneumophila T4BSS and effectors, trying to demonstrate to the readers the cunning survival strategy and the delicate virulent machine of L. pneumophila.
[1] Fraser DW, Tsai TR, Orenstein W, Parkin WE, Beecham HJ, Sharrar RG, Harris J, Mallison GF, Martin SM, McDade JE, Shepard CC, Brachman PS. Legionnaires' disease: description of an epidemic of pneumonia. N Engl J Med, 1977, 297(22): 1189-1197.
[2] McDade JE, Shepard CC, Fraser DW, Tsai TR, Redus MA, Dowdle WR. Legionnaires’ disease: isolation of a bacterium and demonstration of its role in other respiratory disease. N Engl J Med, 1977, 297(22): 1197-1203.
[3] Brenner DJ, Steigerwalt AG, McDade JE. Classification of the Legionnaires' disease bacterium: Legionella pneumophila, genus novum, species nova, of the family Legione-llaceae, familia nova. Ann Intern Med, 1979, 90(4): 656- 658.
[4] 康晓明, 唐忠群, 夏锡荣. 嗜肺军团菌感染一例报告. 解放军医学杂志, 1982, 7(4): 240.
[5] Fields BS, Benson RF, Besser RE. Legionella and Legionnaires' disease: 25 years of investigation. Clin Microbiol Rev, 2002, 15(3): 506-526.
[6] Taylor M, Ross K, Bentham R. Legionella, protozoa, and biofilms: interactions within complex microbial systems. Microb Ecol, 2009, 58(3): 538-547.
[7] Swanson MS, Hammer BK. Legionella pneumophila pathogesesis: a fateful journey from amoebae to macrophages. Annu Rev Microbiol, 2000, 54: 567-613.
[8] Horwitz MA. The Legionnaires' disease bacterium (Legionella pneumophila) inhibits phagosome-lysosome fusion in human monocytes. J Exp Med, 1983, 158(6): 2108-2126.
[9] Vincent CD, Vogel JP. The Dot/Icm type IVB secretion system of Legionella. In: Heuner K, Swanson MS, eds. Legionella: molecular microbiology. Norfolk: Caister Academic Press, 2008.
[10] Segal G, Shuman HA. Intracellular multiplication and human macrophage killing by Legionella pneumophila are inhibited by conjugal components of IncQ plasmid RSF1010. Mol Microbiol, 1998, 30(1): 197-208.
[11] Vogel JP, Andrews HL, Wong SK, Isberg RR. Conjugative transfer by the virulence system of Legionella pneumophila. Science, 1998, 279(5352): 873-876.
[12] Albert-Weissenberger C, Cazalet C, Buchrieser C. Legionella pneumophila-a human pathogen that coevolved with fresh water protozoa. Cell Mol Life Sci, 2007, 64(4): 432-448.
[13] Marra A, Blander SJ, Horwitz MA, Shuman HA. Identification of a Legionella pneumophila locus required for intracellular multiplication in human macrophages. Proc Natl Acad Sci USA, 1992, 89(20): 9607-9611.
[14] Berger KH, Isberg RR. Two distinct defects in intracellular growth complemented by a single genetic locus in Legionella pneumophila. Mol Microbiol, 1993, 7(1): 7-19.
[15] De Buck E, Anné J, Lammertyn E. The role of protein secretion systems in the virulence of the intracellular pathogen Legionella pneumophila. Microbiology, 2007, 153(Pt 12): 3948-3953.
[16] Jacobi S, Heuner K. Description of a putative type I secretion system in Legionella pneumophila. Int J Med Microbiol, 2003, 293(5): 349-358.
[17] Cianciotto NP. Type II secretion: a protein secretion system for all seasons. Trends Microbiol, 2005, 13(12): 581-588.
[18] Hales LM, Shuman HA. Legionella pneumophila contains a type II general secretion pathway required for growth in amoebae as well as for secretion of the Msp protease. Infect Immun, 1999, 67(7): 3662-3666.
[19] Rossier O, Starkenburg SR, Cianciotto NP. Legionella pneumophila type II protein secretion promotes virulence in the A/J mouse model of Legionnaires' disease pneumonia. Infect Immun, 2004, 72(1): 310-321.
[20] DebRoy S, Dao J, Söderberg M, Rossier O, Cianciotto NP. Legionella pneumophila type II secretome reveals unique exoproteins and a chitinase that promotes bacterial persistence in the lung. Proc Natl Acad Sci USA, 2006, 103(50): 19146-19151.
[21] Söderberg MA, Ros
