Аннотация
Многие бактерии выделяют токсины, являющиеся основными факторами вирулентности. Мы остановимся на семи бактериальных токсинах, продуцируемых хорошо известными патогенными микроорганизмами. Эти токсины отличаются различными механизмами действия в макроорганизме и включают: бетта-токсин Staphylococcus aureus, шигеллезный токсин, цитотоксический некротизирующий фактор первого типа, термостабильный токсин кишечной палочки Escherichia coli, ботулотоксин, столбнячный нейротоксин и токсин S.aureus, вызывающий токсический шок. В данной статье будут обсуждены структура и синтез, механизм действия и вклад токсинов в вирулентность, а также роль некоторых из них в передаче сигналов в эукариотических клетках и полезное использование токсинов и анатоксинов (токсоидов). Авторы стремились показать важность изучения бактериальных токсинов как для фундаментальной, так и для прикладной науки.
-
1.
Roux E, Yersin A. Contribution a l'etude de la diphtherie. Ann Inst Pasteur 1888; 629-61.
-
2.
Schlessinger D, Schaechter M. Bacterial toxins. In: Schaechter M, Medoff G, Eigenstein Bl, editors. Mechanisms of microbial disease. 2nd ed. Baltimore: Williams and Wilkins; 1993.p. 162-75.
-
3.
Songer JG. Bacterial phospholipases and their role in virulence. Trends Microbiol 1997;5:156-61.
-
4.
Lottenberg R, Minning-Wenz D, Boyle MD. Capturing host plasmin(ogen): a common mechanism for invasive pathogens? Trends Microbiol 1994;2:20-4.
-
5.
Harrington DJ. Bacterial collagenases and collagendegrading enzymes and their potential role in human disease. Infect Immun 1996;64:1885-91.
-
6.
Bhakdi S, Tranum Jensen J. Alpha-toxin of Staphylococcus aureus. Microbiol Rev 1991;55:733-51.
-
7.
Tomita T, Kamio Y. Molecular biology of the pore-forming cytolysins from Staphylococcus aureus, alpha- and gamma-hemolysins and leukocidin. Biosci Biotechnol Biochem1997;61:565-72.
-
8.
Bhakdi S, Bayley H, Valeva A, Walev I, Walker B, Weller U, et al. Staphylococcal alpha-toxin, streptolysin-O and Escherichia coli hemolysm: prototypes of pore-forming bacterial cytolysins. Arch Microbiol 1996;165:73-9.
-
9.
Song L, Hobaugh MR, Shustak C, Cheley S, Bayley H, Gouaux JE. Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. Science 1996;274:1859-66.
-
10.
Lesieur C, Vecsey Semjen B, Abrami L, Fivaz M, Gisouvan der Goot F.Membrane insertion: the strategies of toxins. Mol Membr Biol 1997;14:45-64.
-
11.
Collier RJ, In: Moss J, Vaughan M, editors. ADP-ribosylating toxins and g proteins. Washington: Am Soc Microbiol; 1990.p.3-19.
-
12.
Wick MJ, Iglewski BH. In: Moss J, Vaughan M, editors. ADP-ribosylating toxins and g proteins. Washington: Am Soc Microbiol; 1990.p.11-43.
-
13.
Endo Y, Tsurugi K, Yutsucio T, Takeda Y, Ogasawara Y, Igarashi K. Site of action of a Vero toxin (VT2) from Escherichia coli. O157:147 and Shiga toxin in eucaryotic ribosomes. Eur J Biochem 198;17l:45-50.
-
14.
Saxena SK, O-Brien AD, Ackerman KJ. Shiga toxin, Shiga-like toxin II variant, and ricin are all single-site RNA N-glycosidases of 28 S RNA when microinjected Xenopus oocytes. J Biol Chem 1989;264:596-601.
-
15.
Tesh VL, O-Brien AD. The pathogenic mechanisms of Shiga toxin and the Shiga-like toxins. Mol Microbiol 1991;5:1817-22.
-
16.
O-Brien AD, Tesh VL, Donohue-RoIfe A, Jackson MP, Oisnes S, Sandvig K, et al. Shiga toxin: biochemistry, genetics, mode of action, and role in pathogenesis. In: Sansonetti PJ, editor. Pathogenesis of shigellosis. 180th ed. Berlin-Heidelberg: Springer-Verlag; 1992.p.66-94.
-
17.
O-Brien AD, Kaper JB. Shiga toxin-producing Escherichia coli: yesterday, today, and tomorrow. In: Kaper JB, O-Brien AD, editors. Escherichia coli O157:H7 and other Shiga toxin-producing E.coli strains. Washington: Am Soc Microbiol; 1998.p.1-11.
-
18.
Melton-Celsa AR, O-Brien AD. Activation of Shiga-like toxins by mouse and human intestinal mucus correlates with virulence of enterohemorrhagic Escherichia coli O91:H21 isolates in orally infected, streptomycin-treated mice. Infect Immun 1996;64:1569-76.
-
19.
Stein PE, Boodhoo A, Tyrell GT, Brunton J, Read RJ. Crystal structure of the cell-binding B oligomer of verotoxin-1 from E coli. Nature 1992;355:748-50.
-
20.
Frasier ME, Chernaia MM, Kozlov YV, James MNG. Crystal structure of the holotoxin from Shigella dysenteriae at 2.5 A resolution. Nature Structural Biol 1994;1:59-64.
-
21.
Sixma TK, Kalk KH, van Zanten BA, Dauter Z, Kingma J, Witholt B, et al. Redefined structure of Escherichia coli heat-labile enterotoxin, a close relative of cholera toxin. J Mol Biol 1993;230:890-918.
-
22.
Stein PE, Boodhoo A, Armstrong GD, Cockle SA, Klein MH, Read RJ. The crystal structure of pertussis toxin. Structure 1994;2:45-57.
-
23.
Suh J-K, Hovde CJ, Robertus JD. Shiga toxin attacks bacterial ribosomes as effectively as eukaryotic ribosomes. Biochemistry 1998;37:9394-8.
-
24.
Centers for Disease Control and Prevention. Addressing emerging infectious disease threats: a prevention strategy for the United States. MMWR Morb Mortal Wkly Rep 1994;43:l-18.
-
25.
O-Brien AD, Lively TA, Chen M, Rothman SW, Formal SB. Escherichia coli O157:H7 strains associated with hemorrhagic colitis in the United States produce a Shigella dysenteriae 1 (Shiga)like cytotoxin. Lancet 1983;i:702.
-
26.
Centers for Disease Control. Isolation of E.coli O157:H7 from sporadic cases of hemorrhagic colitis - United States. MMWR Morb Mortal Wkly Rep 1982;31:580-5.
-
27.
Boyce TG, Swerdlow DL, Griffin PM. Escherichia coli O157:H7 and the hemolytic-uremic syndrome. N Engl J Med 1995;333:364-8.
-
28.
Aktories K. Rho proteins: targets for bacterial toxins. Trends Microbiol 1997;5:282-8.
-
29.
Oswald E, Sugai M, Labigne A, Wu HC, Fiorentini C, Boquet P, et al. Cytotoxic necrotizing factor type 2 produced by virulent Escherichia coli modifies the small GTP-binding proteins Rho involved in assembly of actinstress fibers. Proc Nati Acad Sci USA 1994;91:3814-8.
-
30.
Schmidt G, Sehr P, Wilm M, Selzer J, Mann M, Aktories K. Gin-63 of Rho is deamidated by Escherichia coli cytotoxic necrotizing factor-1. Nature 1997;387:725-9.
-
31.
Flatau G, Lemichez E, Gauthier M, Chardin P, Paris S, Fiorentini C, et al. Toxin-induced activation of the G protein p21 Rho by deamidation of glutamine. Nature 1997;387:729-33.
-
32.
Horiguchi Y, Inouc N, Masuda M, Kashimoto T, Katahira J, Sugimoto N, et al. Bordetella bronchiseptica dermonecrotizing toxin induces reorganization of actin stress fibers through deamidation of Gin-63 of the GTP-binding protein Rho. Proc Nati Acad Sci USA 1997;94:11623-6.
-
33.
Falbo V, Pace T, Picci L, Pizzi E, Caprioli A. Isolation and nucleotide sequence of the gene encoding cytotoxic necrotizing factor 1 of Escherichia coli. Infect Immun 1993;61:4909-14.
-
34.
Blum G, Falbo V, Caprioli A, Hacker J. Gene clusters encoding the cytotoxic necrotizing factor type 1, Prs-fimbriae and -hemolysin form the pathogenicity island II of the uropathogenic Escherichia coli strain J96. FEMS Microbiol Lett 1995;126:189-96.
-
35.
Lemichez E, Flatau G, Bruzzone M, Boquet P, Gauthier M. Molecular localization of the Escherichia coli cytotoxic necrotizing factor CNFI cell-binding and catalytic domains. Mol Microbiol 1997;24:1061-70.
-
36.
DeRycke J, Gonzalez EA, Blanco J, Oswald E, Blanco M,Boivin R Evidence for two types of cytotoxic necrotizingfactor in human and animal clinical isolates of Escherichia coli. J Clin Microbiol 1990;28:694-9.
-
37.
Andreu A, Stapleton AE, Fennell C, Lockman HA, Xercavins M, Fernandez F, et al. Urovirulence determinants in Escherichia coli strains causing prostatitis. J Infect Dis 1997;176:464-9.
-
38.
Nair GB, Takeda Y. The heat stable enterotoxins. Microb Pathog 1998;24:123-31.
-
39.
So M, McCarthy BJ. Nucleotide sequence of transposon Tnl681 encoding a heat-stable toxin (ST) and its identification in enterotoxigenic Escherichia coli strains. Proc Nati Acad Sci USA 1980;77:4011-5.
-
40.
So M, Boyer HW, Betlach M, Falkow S. Molecular cloning of an Escherichia coli plasmid determinant that encodes for the production of heat-stable enterotoxin. J Bacteriol 1976;128:463-72.
-
41.
Giannella RA. Eacherichia coli beat-stable enterotoxins, guanylins, and their receptors: what are they and what do they do? J Lab Clin Med 1995;125:173-81.
-
42.
Singh BR, Li B, Read D. Botulinum versus tetanus neurotoxins: why is botulinum neurotoxin but not tetanus neurotoxin a food poison? Toxicon 1995;33:1541-7.
-
43.
Jahn R, Hanson PI, Otto H, Ahnert Hilger G. Botulinum and tetanus neurotoxins: emerging tools for the study of membrane fusion. Cold Spring Harb Symp Quant Biol 1995;60:329-35.
-
44.
Henderson I, Davis T, Elmore M, Minton NP. The genetic basis of toxin production in Clostridium botulinum and Clostridium tetani. In: Rood JI, McClane BA, Songer JG, Titball RW, editors. The clostridia: molecular biology and pathogenesis. San Diego: Academic Press;1997.p.261-94.
-
45.
Schiavo G, Montecucco C. The structure and mode of action of botulinum and tetanus toxins. In: Rood JI, McClane BA, Songer JG, Titball RW, editors. The clostridia: molecular biology and pathogenesis. San Diego: Academic Press;1997.p.295-322.
-
46.
Kessler KR, Benecke R. Botulinum toxin: from poison toremedy. Neurotoxicology 1997;18:761-70.
-
47.
Halpern JL, Neale EA. Neurospecific binding, internalization and retrograde axonal transport. Curr Top Microbiol Immunol 1995;195:221-41.
-
48.
Arnon SS. Human tetanus and human botulism. In: Rood JI, McClane BA, Songer JG, Titball RW, editors. The clostridia: molecular biology and pathogenesis, San Diego: Academic Press;1997.p.95-115.
-
49.
Rago JV, Schlievert PM. Mechanisms of pathogenesis of staphylococcal and streptococcal superantigens. Curr Top Microbiol Immunol 1998;225:81-97.
-
50.
Lee PK, Schlievert PM. Molecular genetics of pyrogenic exotoxin "superantigens" of Group A streptococci and staphylococcus. Curr Top Microbiol Immunol 1991;174:1-19.
-
51.
Schlievert PM. Searching for superantigens. Immunol Invest 1997;26:283-90.
-
52.
Bohach GA, Stauffacher CV, Ohiendorf DH, Chi Yl, Vath GM, Schlievert PM. The staphylococcal and streptococcal pyrogenic toxin family. In: Singh BR, Tu AT, editors. Natural Toxins II. New York: Plenum Press; 1996.p.131-54.
-
53.
Papageorgiou AC, Acharya KR. Superantigens as immunomodulators: recent structural insights. Structure 1997;5:991-6.
-
54.
Prasad GS, Radhakrishnan R, Mitchell DT, Earhart CA, Dinges MM, Cook WJ, et al. Refined structures of three crystal forms of toxic shock syndrome toxin-I and of a tetramutant with reduced activity. Protein Sci 1997;6:1220-7.
-
55.
Betley MJ, Borst DW, Regassa LB. Staphylococcal enterotoxins, toxic shock syndrome toxin and streptococcal pyrogenic exotoxins: a comparative study of their molecular biology. Chem Immunol 1992;55:1-35.
-
56.
Stevens DL. Superantigens: their role in infectious diseases. Immunol Invest 1997;26:275-81.
-
57.
Harnett MM. Analysis of G-proteins regulating signal transduction pathways. Methods Mol Biol 1994;27:199-211.
-
58.
Bokoch GM, Katada T, Northup JK, Hewlett EL, GilmanAG. Identification of the predominant substrate for ADP-ribosylation by islet activating protein. J Biol Chem 1983;258:2072-5.
-
59.
Neer EJ. Heterotrimeric G proteins: organizers of transmembrane signals. Cell 1995;80:249-57.
-
60.
Snider DP. The mucosal adjuvant activities of ADP-ribosylating bacterial enterotoxins. Crit Rev Immunol 1995;15:317-48.
-
61.
Holmgren J, Lycke N, Czerkinsky C. Cholera toxin and cholera-B subunit as oral mucosal adjuvant and antigen vector systems. Vaccine 1993;11:1179-84.
-
62.
Pastan I. Targeted therapy of cancer with recombinant immunotoxins. Biochim Biophys Acta 1997;1333:01-6.
-
63.
Ghetie MA, Ghetie V, Vitetta ES. Immunotoxins for the treatment of B-cell lymphomas. Mol Med 1997;3:420-7.
-
64.
Winkler U, Barth S, Schnell R, Diehl V, Engert A. The emerging role of immunotoxins in leukemia and lymphoma. Ann Oncol 1997;8:139-46.
-
65.
Murray LJ, Habeshaw JA, Wiels J, Greaves MF. Expression of Burkitt lymphoma-associated antigen(defined by the monoclonal antibody 38.13)on both normal and malignant germinal-centre B cells. Int J Cancer 1985;36:561-5.
-
66.
Taga S, Mangeney M, Tursz T, Wiels J. Differential regulation of glycosphingolipid biosynthesis in phenotypically distinct Burkitt-s lymphoma cell lines. Int J Cancer 1995;61:261-7.
-
67.
LaCasse EC, Saleh MT, Patterson B, Minden MD, Gariepy J. Shiga-like toxin purges human lymphoma from bone marrow of severe combined immunodeficient mice. Blood 1996;88:1551-67.
-
68.
Wheeler AH. Therapeutic uses of botulinum toxin. Am Fam Physician 1997;55:541-8.
-
69.
Averbuch-Heller L, Leigh RJ. Medical treatments for abnormal eye movements: pharmacological, optical and immunological strategies. Aust NZJ Ophthalmol 1997;25:7-13.
-
70.
Carter SR, Seiff SR. Cosmetic botulinum toxin injections. Int Ophthalmol Clin 1997;37:69-79.
-
71.
Maseri A, Andreotti F. Targeting new thrombolytic regimens at specific patient groups: implications for research and cost-containment. Eur Heart J 1997;18:F28-35.
-
72.
Levine SR. Thrombolytic therapy for stroke: the new paradigm. Hosp Pract (Off Ed) 1997;32:57-73.
-
73.
Cherry JD. Comparative efficacy of acellular pertussis vaccines: an analysis of recent trials. Pediatr Infect Dis 1997;16:890-6.
-
74.
National Institutes of Health. The Jordan report: accelerated development of vaccines. 1998.
-
75.
Kraulis PJ. MOLSCRIPT: A program to produce both detailed and schematic plots of protein structures. J Applied Crystallography 1991;24:946-50.