Биологические свойства бактериальных токсинов
https://doi.org/10.35825/2587-5728-2024-8-1-34-64
Аннотация
Знания по биологическим свойствам бактериальных токсинов постоянно обновляются. В последние два десятилетия интерес исследователей смещался в направлении от природных токсинов к их генетически измененным производным. Цель работы – обобщение знаний по биологическим свойствам бактериальных токсинов, накопленных в англоязычной научной литературе за последние годы. Метод исследования – аналитический. Источниковая база исследования – в основном англоязычная научная литература, доступная через глобальную сеть «Интернет». Результаты. В работе рассмотрены: организация и общий механизм действия молекул бактериальных токсинов; достоверность показателей их токсичности, приведенных в научной литературе; токсическое действие токсинов различных групп, различающихся по механизму действия; получение гибридных и модифицированных токсинов; выявление искусственных токсинов. Выводы. Среди бактериальных токсинов наибольшую опасность представляют бинарные токсины. Бинарный состав экзотоксинов бактерий, хорошая изученность их субъединиц, функциональных доменов, механизмов сборки и внутриклеточного действия позволяют вести их модификацию в направлении изменения спектра целей, токсичности, механизма поражающего действия и иммуногенности. Для выявления генетически измененных токсинов, малоизученных аналогов и изоформ природных токсинов могут быть использованы специальные программы, основанные на машинном обучении.
Ключевые слова
Об авторе
М. В. СупотницкийРоссия
Супотницкий Михаил Васильевич. Главный специалист, канд. биол. наук, ст. науч. сотр.
111024, г. Москва, проезд Энтузиастов, д. 1
Список литературы
1. Вертиев ЮВ. Бактериальные токсины: биологическая сущность и происхождение. Журн микробиол эпидемиол иммунобил. 1996;(3):43–6.
2. Бухарин ОВ, Литвин ВЮ. Патогенные бактерии в природных экосистемах. Екатеринбург; 1997.
3. Bezrukov SM, Nestorovich EM. Inhibiting bacterial toxins by channel blockage. Pathog Dis. 2016;74(2):ftv113. https://doi.org/10.1093/femspd/ftv113
4. Rudkin JK, McLoughlin RM, Preston A, Massey RC. Bacterial toxins: Offensive, defensive, or something else altogether? PLoS Pathog. 2017;13(9):e1006452. https://doi.org/10.1371/journal.ppat.1006452
5. Biernbaum EN, Kudva IT. AB5 Enterotoxin-Mediated Pathogenesis: Perspectives Gleaned from Shiga Toxins. Toxins (Basel). 2022;14(1):62. https://doi.org/10.3390/toxins14010062
6. Márquez-López A, Fanarraga ML. AB Toxins as High-Affinity Ligands for Cell Targeting in Cancer Therapy. Int J Mol Sci. 2023;24(13):11227. https://doi.org/10.3390/ijms241311227
7. Bonifacino JS, Rojas R. Retrograde transport from endosomes to the trans-Golgi network. Nat Rev Mol Cell Biol. 2006;7:568–79. https://doi.org/10.1038/nrm1985
8. Sandvig K, Skotland T, van Deurs B, Klokk TI. Retrograde transport of protein toxins through the Golgi apparatus. Histochem Cell Biol. 2013;140:317–326.
9. Lukassen S, Chua R, Trefzer T, Kahn NC, Schneider MA, Muley Th, et al. SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. EMBO J. 2020;39(10):e105114. https://doi.org/10.15252/embj.20105114
10. Finlay B, Falkow S. Common themes in microbial pathogenicity. Microbiol Rev. 1997. 53(2);210–30. https://doi.org/10.1128/mr.53.2.210-230.1989
11. Sanyaolu A, Okorie Ch, Marinkovic A, Haider H. The emerging SARS-CoV-2 variants of concern. Ther Adv Infect Dis. 2021. https://doi.org/10.1177/20499361211024372
12. Littler DR, Ang SY, Moriel DG, Kocan M, Kleifeld O, Johnson MD, et al. Structure-function analyses of a pertussis-like toxin from pathogenic Escherichia coli reveal a distinct mechanism of inhibition of trimeric G-proteins. J Biol Chem. 2017;292(36):15143–58. https://doi.org/10.1074/jbc.M117.796094
13. Lemichez E, Flatau G, Bruzzone M, Boquet P, Gauthier M. Molecular localization of the Escherichia coli cytotoxic necrotizing factor CNF1 cell-binding and catalytic domains. Mol Microbiol. 1997;24(7):1061–70. https://doi.org/10.1046/j.1365-2958.1997.4151781.x
14. Petosa C, Collier P, Klimpel KR, Leppla SH, Liddington RC. Crystal structure of the anthrax toxin protective antigen. Nature. 1997;385(6619):833–38. https://doi.org/10.1038/385833a0
15. Trescos Y, Tournier J-N. Cytoskeleton as an emerging target of anthrax toxins. Toxins. 2012;4:83–97. https://doi.org/10.3390/toxins4020083
16. Zuverink M, Barbieri JT. Protein Toxins That Utilize Gangliosides as Host Receptors. Prog Mol Biol Transl Sci. 2018;156:325–54. https://doi.org/10.1016/bs.pmbts.2017.11.010
17. Uchida I, Ishihara R, Tanaka K, Hata E, Makino SI, Kanno T, et al. Salmonella enterica serotype Typhimurium DT104 ArtA-dependent modification of pertussis toxin-sensitive G proteins in the presence of [32P] NAD. Microbiology (Reading). 2009;155(Pt 11):3710–18. https://doi.org/10.1099/mic.0.028399-0
18. Pavlik BJ, Hruska EJ, Van Cott KE, Blum PH. Retargeting the Clostridium botulinum C2 toxin to the neuronal cytosol. Sci Rep. 2016;6:23707. https://doi.org/10.1038/srep23707
19. Friebe S, van der Goot F, Bürgi J. The Ins and Outs of Anthrax Toxin. Toxins. 2016;8:69. https://doi.org/10.3390/toxins8030069
20. Rossetto O, Montecucco C. Tables of Toxicity of Botulinum and Tetanus Neurotoxins. Toxins (Basel). 2019;11(12):686. https://doi.org/10.3390/toxins11120686
21. Schmitt CK, Meysick KC, Brien AD. Bacterial toxins: friends or foes? Emerg Infect Dis. 1999;5(2):224–34. https://doi.org/10.3201/eid0502.990206
22. Dal Peraro M, van der Goot FG. Pore-forming toxins: ancient, but never really out of fashion. Nat Rev Microbiol. 2016;14(2):77–92. https://doi.org/10.1038/nrmicro.2015.3
23. Berube BJ, Wardenburg J. Staphylococcus aureus α-toxin: nearly a century of intrigue. Toxins (Basel). 2013;5(6):1140–66. https://doi.org/10.3390/toxins5061140
24. Li Y, Li Y, Mengist HM, Zhang C, Wang B, Li T, et al. Structural Basis of the Pore-Forming Toxin/ Membrane. Interaction Toxins (Basel). 2021;13(2):128. https://doi.org/10.3390/toxins13020128
25. Bischofberger M, Iacovache I, van der Goot FG. Pathogenic pore-forming proteins: function and host response. Cell Host Microbe. 2012;12(3):266–75. https://doi.org/10.1016/j.chom.2012.08.005
26. Xiang Y, Yan C, Guo X, Zhou K, Li S, Gao Q, et al. Host-derived, pore-forming toxin-like protein and trefoil factor complex protects the host against microbial infection. Proc Natl Acad Sci USA. 2014;111(18):6702–7. https://doi.org/10.1073/pnas.1321317111
27. Galinier R, Portela J, Moné Y, Allienne JF, Henri H, Delbecq S, et al. Biomphalysin, a new β pore-forming toxin involved in Biomphalaria glabrata immune defense against Schistosoma mansoni. PLoS Pathog. 2013;9(3):e1003216. https://doi.org/10.1371/journal.ppat.1003216
28. Ulhuq FR, Mariano G. Bacterial pore-forming toxins. Microbiology (Reading). 2022;168(3):001154. https://doi.org/10.1099/mic.0.001154
29. Dudev T, Lim C. Ion selectivity in the selectivity filters of acidsensing ion channels. Sci Rep. 2015;5:7864. https://doi.org/10.1038/srep07864
30. Bhakdi S, Bayley H, Valeva A, Walev I, Walker B, Kehoe M, et al. Staphylococcal alpha-toxin, streptolysin-O and Escherichia coli hemolysin: prototypes of pore-forming bacterial cytolysins. Arch Microbiol. 1996;165(1):73–9. https://doi.org/10.1007/s002030050300
31. Bhakdll S, Tranum-Jensen J. Alpha-toxin of Staphylococcus aureus. Microbiol Rev. 1991;55(4):733–51. https://doi.org/10.1128/mr.55.4.733-751.1991
32. Ющук НД, Кулагина МТ. Дифтерия: клиническое течение, диагностика и лечение. Русский меди- цинский журнал. 1997;(4):208–17.
33. Yamaizumi M, Mekada E, Uchida T, Okada Y. One molecule of diphtheria toxin fragment A introduced into a cell can kill the cell. Cell. 1978;15(1):245-50. https://doi.org/10.1016/0092-8674(78)90099-5
34. Liu PV. The roles of various fractions of Pseudomonas aeruginosa in its pathogenesis. 3. Identity of the lethal toxins produced in vitro and in vivo. J Infect Dis. 1966;116(4):481–89. https://doi.org/10.1093/infdis/116.4.481
35. Liu PV. Toxins of Pseudomonas aeruginosa. In: Pseudomonas aeruginosa (clinical manifestation and current therapy). Doggett RG, Ed. N.Y.; 1979. P. 90–135.
36. Мороз АФ, Анциферова НГ, Баскакова НИ. Синегнойная инфекция. Мороз АФ, ред. М.; 1988. Moroz AF, Anciferova NG, Baskakova NI. Pseudomonas infection. Moroz AF, Ed. Moscow; 1988 (in Russian).
37. McCluskey AJ, Collier RJ. Receptor-directed chimeric toxins created by sortase-mediated protein fusion. Mol Cancer Ther. 2013;12(10):2273–81. https://doi.org/10.1158/1535-7163.MCT-13-0358
38. Лазарева АВ, Чеботарь ИВ, Крыжановская ОА, Чеботарь ВИ, Маянский НА. Pseudomonas aeruginosa: патогенность, патогенез и патология. Клин микробиол антимикроб химиотер. 2015;17(3):170–86.
39. Kreitman RJ, Siegall CB, Chaudhary VK, FitzGerald DJ, Pastan I. Properties of chimeric toxins with two recognition domains: interleukin 6 and transforming growth factor alpha at different locations in Pseudomonas exotoxin. Bioconjug Chem. 1992;3(1):63–8. https://doi.org/10.1021/bc00013a010
40. Tian S, Zhou N. Gaining New Insights into Fundamental Biological Pathways by Bacterial Toxin-Based Genetic Screens. Bioengineering (Basel). 2023;10(8):884. https://doi.org/10.3390/bioengineering10080884
41. Chan YS, Ng TB. Shiga toxins: From structure and mechanism to applications. Appl Microbiol Biotechnol. 2016;100:1597–610. https://doi.org/10.1007/s00253-015-7236-3
42. De SN. Enterotoxicity of bacteria-free culture-filtrate of Vibrio cholera. Nature. 1959;183(4674):1533–4. https://doi.org/10.1038/1831533a0
43. Bharati K, Ganguly NK. Cholera toxin: a paradigm of a multifunctional protein. Indian J Med Res. 2011;133(2):179–87. PMID: 21415492.
44. He X, Yang J, Ji M, Chen Y, Chen Y, Li H, et al. Potential delivery system based on cholera toxin: A macromolecule carrier with multiple activities. J Control Release. 2022;343:551–63. https://doi.org/10.1016/j.jconrel.2022.01.050
45. Weiss AA, Hewlett EL, Myers GA, Falkow S. Pertussis toxin and extracytoplasmic adenylate cyclase as virulence factors of Bordetella pertussis. J Infect Dis. 1984;150:219–22. https://doi.org/10.1093/infdis/150.2.2194
46. Gregg KA, Merkel TJ. Pertussis Toxin: A Key Component in Pertussis Vaccines? T oxins ( Basel). 2019;11(10):557. https://doi.org/10.3390/toxins11100557
47. Ernst K. Novel Strategies to Inhibit Pertussis Toxin. Toxins (Basel). 2022;14(3):187. https://doi.org/10.3390/toxins14030187
48. Carbonetti NH. Contribution of Pertussis Toxin to the Pathogenesis of Pertussis Disease. Pathog Dis. 2015;73:ftv073. https://doi.org/10.1093/femspd/ftv073
49. Kilgore PE, Salim AM, Zervos MJ, Schmitt H.-J. Pertussis: Microbiology, Disease, Treatment, and Prevention. Clin Microbiol Rev. 2016;29:449–86. https://doi.org/10.1128/CMR.00083-15
50. Scanlon K, Skerry C, Carbonetti N. Association of Pertussis Toxin with Severe Pertussis Disease. Toxins (Basel). 2019;11(7):373. https://doi.org/10.3390/toxins11070373
51. Saitoh M, Tanaka K, Nishimori K, Makino SI, Kanno T, Ishihara R, et al. The artAB genes encode a putative ADP-ribosyltransferase toxin homologue associated with Salmonella enterica serovar Typhimurium DT104. Microbiology. 2005;151:3089–96. https://doi.org/10.1099/mic.0.27933-0
52. Johnson TJ, DebRoy C, Belton S, Williams ML, Lawrence M, Nolan LK, et al. Pyrosequencing of the Vir Plasmid of Necrotoxigenic Escherichia coli. Vet Microbiol. 2010;144(1–2):100–9. https://doi.org/10.1016/j.vetmic.2009.12.022
53. Scuron MD, Boesze-Battaglia K, Dlakić M, Shenker BJ. The Cytolethal Distending Toxin Contributes to Microbial Virulence and Disease Pathogenesis by Acting As a Tri-Perditious Toxin. Front Cell Infect Microbiol. 2016;6:168. https://doi.org/10.3389/fcimb.2016.00168
54. Lai YR, Chang YF, Ma J, Chiu CH, Kuo ML, Lai CH. From DNA Damage to Cancer Progression: Potential Effects of Cytolethal Distending Toxin. Front Immunol. 2021;12:760451. https://doi.org/10.3389/fimmu.2021.760451
55. Pickett CL, Cottle DL, Pesci EC, Bikah G. Cloning, sequencing, and expression of the Escherichia coli cytolethal distending toxin genes. Infect Immun. 1994;62:1046–51. https://doi.org/10.1128/iai.62.3.1046-1051.1994
56. Grasso F, Frisan T. Bacterial Genotoxins: Merging the DNA Damage Response into Infection Biology. Biomolecules. 2015;5(3):1762–82. https://doi.org/10.3390/biom5031762
57. Ceelen LM, Decostere A, Ducatelle R, Haesebrouck F. Cytolethal distending toxin generates cell death by inducing a bottleneck in the cell cycle. Microbiol Res. 2006;161(2):109–20. https://doi.org/10.1016/j.micres.2005.04.002
58. Guerra L, Cortes-Bratti X, Guidi R, Frisan T. The biology of the cytolethal distending toxins. Toxins (Basel). 2011;3(3):172–90. https://doi.org/10.3390/toxins3030172
59. Nougayrede JP, Taieb F, De Rycke J, Oswald E. Cyclomodulins: Bacterial Effectors That Modulate the Eukaryotic Cell Cycle. Trends Microbiol. 2005;13(3):103–10. https://doi.org/10.1016/j.tim.2005.01.002
60. Pirazzini M, Henke T, Rossetto O, Mahrhold S, Krez N, Rummel A, et al. Neutralisation of specific surface carboxylates speeds up translocation of botulinum neurotoxin type B enzymatic domain. FEBS Lett. 2013;587(23):3831–86. https://doi.org/10.1016/j.febslet.2013.10.010
61. Contreras E, Masuyer G, Qureshi N, Chawla S, Dhillon HS, Lee HL, Chen J, et al. A neurotoxin that specifically targets Anopheles mosquitoes. Nat Commun. 2019;10(1):2869. https://doi.org/10.1038/s41467-019-10732-w
62. Peck MW, Smith TJ, Anniballi F, Austin JW, Bano L, Bradshaw M, et al. Historical perspectives and guidelines for botulinum neurotoxin subtype nomenclature. Toxins. 2017;9:38. https://doi.org/10.3390/toxins9010038
63. Rosales RL, Bigalke H, Dressler D. Pharmacology of botulinum toxin: differences between type A preparations. Eur J Neurol. 2006;Suppl 1:2–10. https://doi.org/10.1111/j.1468-1331.2006.01438.x
64. Megighian A, Pirazzini M, Fabris F, Rossetto O, Montecucco C. Tetanus and tetanus neurotoxin: from peripheral uptake to central nervous tissue targets. J Neurochem. 2021;158:1244–1253. https://doi.org/10.1111/jnc.15330
65. Rao AK, Sobel J, Chatham-Stephens K, Luquez C. Clinical guidelines for diagnosis and treatment of botulism. MMWR Recommendations Rep. 2021;70:1–30. https://www.cdc.gov/mmwr/volumes/70/rr/rr7002a1.htm
66. Плецитный ДФ. Экспериментальное изучение патогенеза столбнячной интоксикации. М.; 1958. Plecitnyj DF. Experimental study of the pathogenesis of tetanus intoxication. Moscow; 1958 (in Russian).
67. Arnon S. Human tetanus and human botulism. In: The clostridia: molecular biology and pathogenesis. Rood JI, McClane BA, Songer JG, Titball RW, Eds. San Diego: Academic Press; 1997. P. 95–115. https://doi.org/10.1146/annurev-biochem-013118-111654
68. Dong M, Masuyer G, Stenmark P. Botulinum and tetanus neurotoxins. Annu Rev Biochem. 2019;88:811–37. https://doi.org/10.1146/annurev-biochem-013118-111654
69. Halpern J, Neale E. Neurospecific binding, internalization and retrograde axonal transport. Curr Top Microbiol Immunol. 1995;195(1):221–41. https://doi.org/10.1007/978-3-642-85173-5_10
70. Doxey AC, Mansfeld MJ, Montecucco C. Discovery of novel bacterial toxins by genomics and computational biology. Toxicon. 2018;147:2–12. https://doi.org/10.1016/j.toxicon.2018.02.002
71. Montecucco C, Molgó J. Botulinal neurotoxins: revival of an old killer. Curr Opin Pharmacol. 2005;5(3):274–279. https://doi.org/10.1016/j.coph.2004.12.006
72. Шихкеримов РК, Истомина ЕВ. Рекомбинантные ботулотоксины как новый этап развития ботулинотерапии. Возможности и перспективы применения в неврологической практике. Неврология, нейропсихиатрия, психосоматика. 2022;14(6): 103–9.
73. White J, Herman A, Pullen AM, Hashimoto K, Sugaya K, Kubo M, et al. The Vβ-specific superantigen staphylococcal enterotoxin B: Stimulation of mature T cells and clonal deletion in neonatal mice. Cell. 1989;56:27–35. https://doi.org/10.1016/0092-8674(89)90980-x
74. Schlievert P. Searching for superantigens. Immunol Infect. 1997;26(2):283–90. https://doi.org/10.3109/08820139709048934
75. Blank C, Luz A, Bendigs S, Erdmann A, Wagner H, Heeg K. Superantigen and endotoxin synergize in the induction of lethal shock. Eur J Immunol. 1997;27(4):825–33. https://doi.org/10.1002/eji.1830270405
76. Sutkowski N, Conrad B, Thorley-Lawson D.A, Huber BT. Epstein-Barr virus transactivates the human endogenous retrovirus HERV-K18 that encodes a superantigen. Immunity. 2001;15(4):579–89. https://doi.org/10.1016/s1074-7613(01)00210-2
77. Efremenko E, Aslanli A, Lyagin I. Advanced Situation with Recombinant Toxins: Diversity, Production and Application Purposes. Int J Mol Sci. 2023;24(5):4630. https://doi.org/10.3390/ijms24054630
78. Deist BR, Rausch MA, Fernandez-Luna MT, Adang MJ, Bonning BC. Bt toxin modification for enhanced efficacy. Toxins (Basel). 2014;6(10):3005–27. https://doi.org/10.3390/toxins6103005
79. Шамсутдинов АФ, Тюрин ЮА. Белковые токсины Staphylococcus aureus. Журнал микробиологии, эпидемиологии и иммунобиологии. 2014;91(2):113–20.
80. Wu SJ, Koller CN, Miller DL, Bauer LS, Dean DH. Enhanced toxicity of Bacillus thuringiensis Cry3A deltaendotoxin in coleopterans by mutagenesis in a receptor binding loop. FEBS Lett. 2000;473:227–32. https://doi.org/10.1016/s0014-5793(00)01505-2
81. Liu XS, Dean DH. Redesigning Bacillus thuringiensis Cry1Aa toxin into a mosquito toxin. Prot Eng Design Selec. 2006;19:107–11. https://doi.org/10.1093/protein/gzj009
82. Brin MF, Lew MF, Adler CH, Comella CL, Factor SA, Jankovic J, et al. Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia. Neurology. 1999; 53(7):1431–38. https://doi.org/10.1212/wnl.53.7.1431
83. Pappert EJ, Germanson T. Myobloc/Neurobloc European Cervical Dystonia Study Group. Botulinum toxin type B vs. type A in toxin-naïve patients with cervical dystonia: Randomized, double-blind, noninferiority trial. Mov Disord. 2008;23(4):510–17. https://doi.org/10.1002/mds.21724
84. Tao L, Peng L, Berntsson RP, Liu SM, Park S, Yu F, et al. Engineered botulinum neurotoxin B with improved efficacy for targeting human receptors. Nat Commun. 2017;8(1):53. https://doi.org/10.1038/s41467-017-00064-y
85. Antignani A, Ho E, Bilotta MT, Qiu R, Sarnvosky R, FitzGerald DJ. Targeting Receptors on Cancer Cells with Protein Toxins. Biomolecules. 2020;10(9):1331. https://doi.org/10.3390/biom10091331
86. Kiyokawa T, Shirono K, Hattori T, Nishimura H, Yamaguchi K, Nichols JC, et al. Cytotoxicity of interleukin 2-toxin toward lymphocytes from patients with adult T-cell leukemia. Cancer Res. 1989;49(14):4042–46. PMID: 2786749.
87. Ardini M, Vago R, Fabbrini MS, Ippoliti R. From Immunotoxins to Suicide Toxin Delivery Approaches: Is There a Clinical Opportunity? Toxins (Basel). 2022;14(9):579. https://doi.org/doi:10.3390/toxins14090579
88. Contet A, Caussanel V, Beck A, Lowe P. Immunotoxines et immunocytokines [Immunotoxins and immunocytokines]. Med Sci (Paris). 2019;35(12):1054–61 (in French). https://doi.org/10.1051/medsci/2019205
89. Kreitman RJ, Siegall CB, Chaudhary VK, FitzGerald DJ, Pastan I. Properties of chimeric toxins with two recognition domains: interleukin 6 and transforming growth factor alpha at different locations in Pseudomonas exotoxin. Bioconjug Chem. 1992;3(1):63–8. https://doi.org/10.1021/bc00013a010
90. Fujinaga Y, Wolf AA, Rodighiero C. Gangliosides that associate with lipid rafts mediate transport of cholera and related toxins from the plasma membrane to endoplasmic reticulm. Mol Biol Cell. 2003;14:4783–93. http://dx.doi.org/10.1091/mbc
91. Guimaraes CP, Carette JE, Varadarajan M, Antos J, Popp MW, Spooner E, et al. Identification of host cell factors required for intoxication through use of modified cholera toxin. J Cell Biol. 2011;195(5):751–64. https://doi.org/10.1083/jcb.201108103
92. Avarbock AB, Loren AW, Park JY, Junkins-Hopkins JM, Choi J, Litzky LA, et al. Lethal vascular leak syndrome after denileukin diftitox administration to a patient with cutaneous gamma/delta T-cell lymphoma and occult cirrhosis. Am J Hematol. 2008;83(7):593–5. https://doi.org/10.1002/ajh.21180
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Для цитирования:
Супотницкий М.В. Биологические свойства бактериальных токсинов. Вестник войск РХБ защиты. 2024;8(1):34-64. https://doi.org/10.35825/2587-5728-2024-8-1-34-64
For citation:
Supotnitskiy M.V. The Biological Properties of Bacterial Toxins. Journal of NBC Protection Corps. 2024;8(1):34-64. (In Russ.) https://doi.org/10.35825/2587-5728-2024-8-1-34-64