中国修复重建外科杂志

中国修复重建外科杂志

胞外囊泡在细菌致病机制中作用的研究进展

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目的 对细菌来源的胞外囊泡(extracellular vesicles,EVs)所含生物活性物质及其在介导细菌-细菌间和细菌-宿主间相互作用中的机制进行综述,并分析其对临床植入物感染防治的指导意义。 方法 广泛查阅近年来国内外细菌来源 EVs 相关的文献,并进行分析和总结。 结果 无论是革兰阴性菌(G 菌)还是革兰阳性菌(G+ 菌)都能分泌包含了多种生物活性物质(如蛋白质、脂质、核酸和毒力因子)的 EVs,可以介导细菌-细菌间和细菌-宿主间的相互作用,并在细菌的致病机制和生物膜形成等方面发挥了重要作用。 结论 细菌来源的 EVs 包含的生物活性物质,在细菌感染性疾病的致病机制中发挥着重要作用。深入研究和理解其致病机制,可以为临床早期诊断、预防和治疗植入物感染等提供新思路。但目前该领域研究还处于初级阶段,相关机制尚需深入研究。

Objective To summarize the bioactive substances contained in bacterial extracellular vesicles (EVs) and their mechanisms in mediating bacterial-bacterial and bacterial-host interactions, as well as their mechanisms for use in implant infection-associated clinical guidance. Methods A wide range of publications on bacterial-derived EVs were extensively reviewed, analyzed, and summarized. Results Both gram-negative bacteria (G bacteria) and gram-positive bacteria (G+ bacteria) can secrete EVs which contain a variety of bioactive substances, including proteins, lipids, nucleic acids, and virulence factors, and mediate bacterial-bacterial and bacterial-host interactions. EVs play an important role in the pathogenic mechanism of bacteria. Conclusion Bioactive substances contained within bacteria-derived EVs play an important role in the pathogenesis of bacterial infectious diseases. In-depth study and understanding of their pathogenic mechanisms can provide new insights which will improve early clinical diagnosis, prevention, and treatment of implant-associated infection. However, at present, research in this area is still in its infancy, and many more in-depth mechanisms need to be further studied.

关键词: 胞外囊泡; 外泌体; 感染; 革兰阴性菌; 革兰阳性菌; 致病机制

Key words: Extracellular vesicles; exosomes; infection; gram-negative bacteria; gram-positive bacteria; pathogenic mechanism

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1. Deatherage BL, Cookson BT. Membrane vesicle release in bacteria, eukaryotes, and archaea: a conserved yet underappreciated aspect of microbial life. Infect Immun, 2012, 80(6): 1948-1957.
2. Choi DS, Kim DK, Kim YK, et al. Proteomics of extracellular vesicles: Exosomes and ectosomes. Mass Spectrom Rev, 2015, 34(4): 474-490.
3. Kim DK, Kang B, Kim OY, et al. EVpedia: an integrated database of high-throughput data for systemic analyses of extracellular vesicles. J Extracell Vesicles, 2013, 2. doi: 10.3402/jev.v2i0.20384. eCollection 2013.
4. Rivera J, Cordero RJ, Nakouzi AS, et al. Bacillus anthracis produces membrane-derived vesicles containing biologically active toxins. Proc Natl Acad Sci U S A, 2010, 107(44): 19002-19007.
5. Lee EY, Choi DY, Kim DK, et al. Gram-positive bacteria produce membrane vesicles: proteomics-based characterization of Staphylococcus aureus-derived membrane vesicles. Proteomics, 2009, 9(24): 5425-5436.
6. Schrempf H, Koebsch I, Walter S, et al. Extracellular Streptomyces vesicles: amphorae for survival and defence. Microb Biotechnol, 2011, 4(2): 286-299.
7. Lee T, Jun SH, Choi CW, et al. Salt stress affects global protein expression profiles of extracellular membrane-derived vesicles of Listeria monocytogenes. Microb Pathog, 2018, 115: 272-279.
8. Jiang Y, Kong Q, Roland KL, et al. Membrane vesicles of Clostridium perfringens type A strains induce innate and adaptive immunity. Int J Med Microbiol, 2014, 304(3-4): 431-443.
9. Brown L, Kessler A, Cabezas-Sanchez P, et al. Extracellular vesicles produced by the Gram-positive bacterium Bacillus subtilis are disrupted by the lipopeptide surfactin. Mol Microbiol, 2014, 93(1): 183-198.
10. Liao S, Klein MI, Heim KP, et al. Streptococcus mutans extracellular DNA is upregulated during growth in biofilms, actively released via membrane vesicles, and influenced by components of the protein secretion machinery. J Bacteriol, 2014, 196(13): 2355-2366.
11. Olaya-Abril A, Prados-Rosales R, McConnell MJ, et al. Characterization of protective extracellular membrane-derived vesicles produced by Streptococcus pneumoniae. J Proteomics, 2014, 106: 46-60.
12. MacDonald IA, Kuehn MJ. Offense and defense: microbial membrane vesicles play both ways. Res Microbiol, 2012, 163(9-10): 607-618.
13. Choi DS, Kim DK, Kim YK, et al. Proteomics, transcriptomics and lipidomics of exosomes and ectosomes. Proteomics, 2013, 13(10-11): 1554-1571.
14. Huang W, Wang S, Yao Y, et al. Employing Escherichia coli-derived outer membrane vesicles as an antigen delivery platform elicits protective immunity against Acinetobacter baumannii infection. Sci Rep, 2016, 6: 37242.
15. Chatterjee SN, Das J. Electron microscopic observations on the excretion of cell-wall material by Vibrio cholerae. J Gen Microbiol, 1967, 49(1): 1-11.
16. Kadurugamuwa JL, Beveridge TJ. Membrane vesicles derived from Pseudomonas aeruginosa and Shigella flexneri can be integrated into the surfaces of other gram-negative bacteria. Microbiology, 1999, 145(Pt 8): 2051-2060.
17. Manning AJ, Kuehn MJ. Functional advantages conferred by extracellular prokaryotic membrane vesicles. J Mol Microbiol Biotechnol, 2013, 23(1-2): 131-141.
18. Manning AJ, Kuehn MJ. Contribution of bacterial outer membrane vesicles to innate bacterial defense. BMC Microbiol, 2011, 11: 258.
19. Roier S, Zingl FG, Cakar F, et al. Bacterial outer membrane vesicle biogenesis: a new mechanism and its implications. Microb Cell, 2016, 3(6): 257-259.
20. Lee EY, Choi DS, Kim KP, et al. Proteomics in gram-negative bacterial outer membrane vesicles. Mass Spectrom Rev, 2008, 27(6): 535-555.
21. Kulkarni HM, Jagannadham MV. Biogenesis and multifaceted roles of outer membrane vesicles from Gram-negative bacteria. Microbiology, 2014, 160(Pt 10): 2109-2121.
22. Horstman AL, Kuehn MJ. Enterotoxigenic Escherichia coli secretes active heat-labile enterotoxin via outer membrane vesicles. J Biol Chem, 2000, 275(17): 12489-12496.
23. Chowdhury C, Jagannadham MV. Virulence factors are released in association with outer membrane vesicles of Pseudomonas syringae pv. tomato T1 during normal growth. Biochim Biophys Acta, 2013, 1834(1): 231-239.
24. Kuehn MJ, Kesty NC. Bacterial outer membrane vesicles and the host-pathogen interaction. Genes Dev, 2005, 19(22): 2645-2655.
25. Dorward DW, Garon CF, Judd RC. Export and intercellular transfer of DNA via membrane blebs of Neisseria gonorrhoeae. J Bacteriol, 1989, 171(5): 2499-2505.
26. Kolling GL, Matthews KR. Export of virulence genes and Shiga toxin by membrane vesicles of Escherichia coli O157:H7. Appl Environ Microbiol, 1999, 65(5): 1843-1848.
27. Mashburn-Warren LM, Whiteley M. Special delivery: vesicle trafficking in prokaryotes. Mol Microbiol, 2006, 61(4): 839-846.
28. Jacobson ES, Ikeda R. Effect of melanization upon porosity of the cryptococcal cell wall. Med Mycol, 2005, 43(4): 327-333.
29. Wolf JM, Espadas-Moreno J, Luque-Garcia JL, et al. Interaction of Cryptococcus neoformans extracellular vesicles with the cell wall. Eukaryot Cell, 2014, 13(12): 1484-1493.
30. Kopecká M, Gabriel M, Takeo K, et al. Microtubules and actin cytoskeleton in Cryptococcus neoformans compared with ascomycetous budding and fission yeasts. Eur J Cell Biol, 2001, 80(4): 303-311.
31. Albuquerque PC, Nakayasu ES, Rodrigues ML, et al. Vesicular transport in Histoplasma capsulatum: an effective mechanism for trans-cell wall transfer of proteins and lipids in ascomycetes. Cell Microbiol, 2008, 10(8): 1695-1710.
32. Rodrigues ML, Nimrichter L, Oliveira DL, et al. Vesicular polysaccharide export in Cryptococcus neoformans is a eukaryotic solution to the problem of fungal trans-cell wall transport. Eukaryot Cell, 2007, 6(1): 48-59.
33. Oliveira DL, Nakayasu ES, Joffe LS, et al. Characterization of yeast extracellular vesicles: evidence for the participation of different pathways of cellular traffic in vesicle biogenesis. PLoS One, 2010, 5(6): e11113.
34. Unal CM, Schaar V, Riesbeck K. Bacterial outer membrane vesicles in disease and preventive medicine. Semin Immunopathol, 2011, 33(5): 395-408.
35. Bomberger JM, Maceachran DP, Coutermarsh BA, et al. Long-distance delivery of bacterial virulence factors by Pseudomonas aeruginosa outer membrane vesicles. PLoS Pathog, 2009, 5(4): e1000382.
36. Ellis TN, Leiman SA, Kuehn MJ. Naturally produced outer membrane vesicles from Pseudomonas aeruginosa elicit a potent innate immune response via combined sensing of both lipopolysaccharide and protein components. Infect Immun, 2010, 78(9): 3822-3831.
37. Soult MC, Dobrydneva Y, Wahab KH, et al. Outer membrane vesicles alter inflammation and coagulation mediators. J Surg Res, 2014, 192(1): 134-142.
38. Kim JH, Yoon YJ, Lee J, et al. Outer membrane vesicles derived from Escherichia coli up-regulate expression of endothelial cell adhesion molecules in vitro and in vivo. PLoS One, 2013, 8(3): e59276.
39. Sharpe SW, Kuehn MJ, Mason KM. Elicitation of epithelial cell-derived immune effectors by outer membrane vesicles of nontypeable Haemophilus influenzae. Infect Immun, 2011, 79(11): 4361-4369.
40. Bauman SJ, Kuehn MJ. Purification of outer membrane vesicles from Pseudomonas aeruginosa and their activation of an IL-8 response. Microbes Infect, 2006, 8(9-10): 2400-2408.
41. Vanaja SK, Russo AJ, Behl B, et al. Bacterial outer membrane vesicles mediate cytosolic localization of LPS and Caspase-11 activation. Cell, 2016, 165(5): 1106-1119.
42. Park KS, Choi KH, Kim YS, et al. Outer membrane vesicles derived from Escherichia coli induce systemic inflammatory response syndrome. PLoS One, 2010, 5(6): e11334.
43. Shah B, Sullivan CJ, Lonergan NE, et al. Circulating bacterial membrane vesicles cause sepsis in rats. Shock, 2012, 37(6): 621-628.
44. Schaar V, de Vries SP, Perez Vidakovics ML, et al. Multicomponent Moraxella catarrhalis outer membrane vesicles induce an inflammatory response and are internalized by human epithelial cells. Cell Microbiol, 2011, 13(3): 432-449.
45. Lee JC, Lee EJ, Lee JH, et al. Klebsiella pneumoniae secretes outer membrane vesicles that induce the innate immune response. FEMS Microbiol Lett, 2012, 331(1): 17-24.
46. Park KS, Lee J, Jang SC, et al. Pulmonary inflammation induced by bacteria-free outer membrane vesicles from Pseudomonas aeruginosa. Am J Respir Cell Mol Biol, 2013, 49(4): 637-645.
47. Wai SN, Lindmark B, Söderblom T, et al. Vesicle-mediated export and assembly of pore-forming oligomers of the enterobacterial ClyA cytotoxin. Cell, 2003, 115(1): 25-35.
48. Kato S, Kowashi Y, Demuth DR. Outer membrane-like vesicles secreted by Actinobacillus actinomycetemcomitans are enriched in leukotoxin. Microb Pathog, 2002, 32(1): 1-13.
49. Hozbor D, Rodriguez ME, Fernández J, et al. Release of outer membrane vesicles from Bordetella pertussis. Curr Microbiol, 1999, 38(5): 273-278.
50. Galka F, Wai SN, Kusch H, et al. Proteomic characterization of the whole secretome of Legionella pneumophila and functional analysis of outer membrane vesicles. Infect Immun, 2008, 76(5): 1825-1836.
51. Chutkan H, Kuehn MJ. Context-dependent activation kinetics elicited by soluble versus outer membrane vesicle-associated heat-labile enterotoxin. Infect Immun, 2011, 79(9): 3760-3769.
52. Chen DJ, Osterrieder N, Metzger SM, et al. Delivery of foreign antigens by engineered outer membrane vesicle vaccines. Proc Natl Acad Sci U S A, 2010, 107(7): 3099-3104.
53. Klimentová J, Stulík J. Methods of isolation and purification of outer membrane vesicles from gram-negative bacteria. Microbiol Res, 2015, 170: 1-9.
54. Ellis TN, Kuehn MJ. Virulence and immunomodulatory roles of bacterial outer membrane vesicles. Microbiol Mol Biol Rev, 2010, 74(1): 81-94.
55. Kim OY, Hong BS, Park KS, et al. Immunization with Escherichia coli outer membrane vesicles protects bacteria-induced lethality via Th1 and Th17 cell responses. J Immunol, 2013, 190(8): 4092-4102.
56. Acevedo R, Fernández S, Zayas C, et al. Bacterial outer membrane vesicles and vaccine applications. Front Immunol, 2014, 5: 121.
57. Norheim G, Tunheim G, Næss LM, et al. An outer membrane vesicle vaccine for prevention of serogroup A and W-135 meningococcal disease in the African meningitis belt. Scand J Immunol, 2012, 76(2): 99-107.
58. Im H, Lee S, Soper SA, et al. Staphylococcus aureus extracellular vesicles (EVs): surface-binding antagonists of biofilm formation. Mol Biosyst, 2017, 13(12): 2704-2714.
59. Chebotar IV, Konchakova ED, Maianskii AN. Vesicle formation as a result of interaction between polymorphonuclear neutrophils and Staphylococcus aureus biofilm. J Med Microbiol, 2013, 62(Pt 8): 1153-1159.
60. Yonezawa H, Osaki T, Kurata S, et al. Outer membrane vesicles of Helicobacter pylori TK1402 are involved in biofilm formation. BMC Microbiol, 2009, 9: 197.
61. Renelli M, Matias V, Lo RY, et al. DNA-containing membrane vesicles of Pseudomonas aeruginosa PAO1 and their genetic transformation potential. Microbiology, 2004, 150(Pt 7): 2161-2169.
62. Corboy MJ, Draper RK. Elevation of vacuolar pH inhibits the cytotoxic activity of furin-cleaved exotoxin A. Infect Immun, 1997, 65(6): 2240-2242.
63. Mashburn LM, Whiteley M. Membrane vesicles traffic signals and facilitate group activities in a prokaryote. Nature, 2005, 437(7057): 422-425.
64. Jang SC, Kim SR, Yoon YJ, et al. In vivo kinetic biodistribution of nano-sized outer membrane vesicles derived from bacteria. Small, 2015, 11(4): 456-461.
65. Kahn ME, Barany F, Smith HO. Transformasomes: specialized membranous structures that protect DNA during Haemophilus transformation. Proc Natl Acad Sci U S A, 1983, 80(22): 6927-6931.
66. Bitto NJ, Chapman R, Pidot S, et al. Bacterial membrane vesicles transport their DNA cargo into host cells. Sci Rep, 2017, 7(1): 7072.
67. Tan TT, Morgelin M, Forsgren A, et al. Haemophilus influenzae survival during complement-mediated attacks is promoted by Moraxella catarrhalis outer membrane vesicles. J Infect Dis, 2007, 195(11): 1661-1670.
68. McBroom AJ, Kuehn MJ. Release of outer membrane vesicles by Gram-negative bacteria is a novel envelope stress response. Mol Microbiol, 2007, 63(2): 545-558.
69. Ciofu O, Beveridge TJ, Kadurugamuwa J, et al. Chromosomal beta-lactamase is packaged into membrane vesicles and secreted from Pseudomonas aeruginosa. J Antimicrob Chemother, 2000, 45(1): 9-13.
70. Kadurugamuwa JL, Beveridge TJ. Bacteriolytic effect of membrane vesicles from Pseudomonas aeruginosa on other bacteria including pathogens: conceptually new antibiotics. J Bacteriol, 1996, 178(10): 2767-2774.
71. Vasilyeva NV, Tsfasman IM, Suzina NE, et al. Secretion of bacteriolytic endopeptidase L5 of Lysobacter sp. XL1 into the medium by means of outer membrane vesicles. FEBS J, 2008, 275(15): 3827-3835.
72. Nevot M, Deroncelé V, Messner P, et al. Characterization of outer membrane vesicles released by the psychrotolerant bacterium Pseudoalteromonas antarctica NF3. Environ Microbiol, 2006, 8(9): 1523-1533.
73. Roden JA, Wells DH, Chomel BB, et al. Hemin binding protein C is found in outer membrane vesicles and protects Bartonella henselae against toxic concentrations of hemin. Infect Immun, 2012, 80(3): 929-942.
74. Murphy TF, Parameswaran GI. Moraxella catarrhalis, a human respiratory tract pathogen. Clinical Infectious Diseases, 2009, 49: 124-131.
75. Simon J, Kotloff K. New and candidate vaccines for gastrointestinal infections. Curr Opin Gastroenterol, 2010, 26(1): 12-16.
76. Gerritzen MJH, Martens DE, Wijffels RH, et al. Bioengineering bacterial outer membrane vesicles as vaccine platform. Biotechnol Adv, 2017, 35(5): 565-574.
77. Petersen H, Nieves W, Russell-Lodrigue K, et al. Evaluation of a Burkholderia pseudomallei outer membrane vesicle vaccine in nonhuman primates. Procedia Vaccinol, 2014, 8: 38-42.
78. Roier S, Leitner DR, Iwashkiw J, et al. Intranasal immunization with nontypeable Haemophilus influenzae outer membrane vesicles induces cross-protective immunity in mice. PLoS One, 2012, 7(8): e42664.
79. Roier S, Fenninger JC, Leitner DR, et al. Immunogenicity of Pasteurella multocida and Mannheimia haemolytica outer membrane vesicles. Int J Med Microbiol, 2013, 303(5): 247-256.
80. Moskowitz SM, Foster JM, Emerson J, et al. Clinically feasible biofilm susceptibility assay for isolates of Pseudomonas aeruginosa from patients with cystic fibrosis. J Clin Microbiol, 2004, 42(5): 1915-1922.
81. Chen Q, Rozovsky S, Chen W. Engineering multi-functional bacterial outer membrane vesicles as modular nanodevices for biosensing and bioimaging. Chem Commun (Camb), 2017, 53(54): 7569-7572.
82. Kadurugamuwa JL, Beveridge TJ. Delivery of the non-membrane-permeative antibiotic gentamicin into mammalian cells by using Shigella flexneri membrane vesicles. Antimicrob Agents Chemother, 1998, 42(6): 1476-1483.
83. Yaron S, Kolling GL, Simon L, et al. Vesicle-mediated transfer of virulence genes from Escherichia coli O157:H7 to other enteric bacteria. Appl Environ Microbiol, 2000, 66(10): 4414-4420.
84. Stevenson TC, Cywes-Bentley C, Moeller TD, et al. Immunization with outer membrane vesicles displaying conserved surface polysaccharide antigen elicits broadly antimicrobial antibodies. Proc Natl Acad Sci U S A, 2018, 115(14): E3106-E3115.