Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/93095
標題: Functional Analysis of CdtABC Toxin from Avibacterium paragallinarum and Its Application 
to Vaccine Development
雞傳染性鼻炎菌 CdtABC 毒素之功能分析及其在疫苗研發之應用
作者: 林佳君
Chia-Chun Lin
關鍵字: 雞傳染性鼻炎菌
細胞致死腫脹毒素
Avibacterium paragallinarum
CdtABC
引用: 中文文獻 1. 何儀香. 雞傳染性鼻炎菌絲狀血球凝集素基因之分析與疫苗之運用. 中興 大學獸醫微生物學研究所學位論文. 1-70, 2012. 2. 林茂勇,宋華聰: 禽病诊治(第二版), 藝軒圖書出版社, 2006. 3. 陳意超. 雞傳染性鼻炎菌 cdtABC 毒素蛋白基因之發現與功能分析. 中 興大學微生物暨公共衛生學研究所學位論文. 1-54, 2013. 4. 陳秉誼. 雞傳染性鼻炎菌莢膜生合成基因之分析與重組次單位疫苗之研 究. 中興大學獸醫微生物學研究所學位論文. 1-75, 2009. 英文文獻 1. Abascal EN, Guerra AC, Vazquez AS, Tenorio VR, Cruz CV, Zenteno E, Contreras GP, Pacheco SV. Identification of iron-acquisition proteins of Avibacterium paragallinarum. Avian Pathol. 38:209-213, 2009. 2. Barnard TG, Van Heerden E, Bragg RR, Albertyn J. Haemophilus paragallinarum haemagglutinin: role in adhesion, serotyping and pathogenicity. The Onderstepoort Journal of Veterinary Research. 75:11-16, 2008. 3. Blackall PJ. The avian haemophili. Clinical Microbiology Reviews. 2:270-277, 1989. 4. Blackall PJ. Infectious coryza: overview of the disease and new diagnostic options. Clinical Microbiology Reviews. 12:627-632, 1999. 5. Blackall PJ, Eaves LE, Aus G. Serotyping of Haemophilus paragallinarum by the Page scheme: comparison of the use of agglutination and hemagglutination-inhibition tests. Avian Diseases. 34:643-645, 1990. 6. Blackall PJ, Eaves LE, Rogers DG. Proposal of a new serovar and altered nomenclature for Haemophilus paragallinarum in the Kume hemagglutinin scheme. Journal of Clinical Microbiology. 28:1185-1187, 1990. 7. Blackall PJ, Morrow CJ, McInnes A, Eaves LE, Rogers DG. Epidemiologic studies on infectious coryza outbreaks in northern New South Wales, Australia, using serotyping, biotyping, and chromosomal DNA restriction endonuclease analysis. Avian Diseases. 34:267-276, 1990. 8. Blackall PJ, Reid GG. Further characterization of Haemophilus paragallinarum and Haemophilus avium. Veterinary Microbiology. 7:359-367, 1982. 9. Blackall PJ, Silva EN, Yamaguchi T, Iritani Y. Characterization of isolates of avian haemophili from Brazil. Avian Diseases. 38:269-274, 1994. 10. Blackall PJ CH, Beckenham T, Blackall LL, and Bisgaard M. Reclassification of Pasteurella gallinarum, [Haemophilus] paragallinarum, Pasteurella avium and Pasteurella volantium as Avibacterium gallinarum gen. nov., comb. nov., Avibacterium paragallinarum comb. nov., Avibacterium avium comb. nov. and Avibacterium volantium comb. nov. Int J Syst Evol Microbiol. 55:353-362, 2005. 11. Bragg RR. Virulence of South African isolates of Haemophilus paragallinarum. Part 1: NAD-dependent field isolates. The Onderstepoort Journal of Veterinary Research. 69:163-169, 2002. 12. Bragg RR, Coetzee L, Verschoor JA. Changes in the incidences of the different serovars of Haemophilus paragallinarum in South Africa: a possible explanation for vaccination failures. Onderstepoort J Vet Res. 63:217-226, 1996. 13. Calderón EN, Thomas K, Morales-Erasto V, Salgado-Miranda C, Soriano-Vargas E. Identification of Avibacterium paragallinarum serovar B-1 from severe infectious coryza outbreaks in Panama. Avian Diseases. 54:1095-1097, 2010. 14. Chen YC, Tan DH, Shien JH, Hsieh MK, Yen TY, Chang PC. Identification and functional analysis of the cytolethal distending toxin gene from Avibacterium paragallinarum. Avian Pathol. 43:43-50, 2014. 15. Chiang YT, Shien JH, Tan DH, Shieh MK, Liu CC, Chen YS, Chang PC. Identification of the lic1ABCD operon that controls the phase-variable expression of phosphorylcholine on lipopolysaccharide from Avibacterium paragallinarum. Avian Pathol. 42:72-78, 2013. 16. Chung JY, Zhang Y, Adler B. The capsule biosynthetic locus of Pasteurella multocida A:1. FEMS Microbiol Lett. 166:289-296, 1998. 17. Cope LD, Lumbley S, Latimer JL, Klesney-Tait J, Stevens MK, Johnson LS, Purven M, Munson RS, Jr., Lagergard T, Radolf JD, Hansen EJ. A diffusible cytotoxin of Haemophilus ducreyi. Proc Natl Acad Sci U S A. 94:4056-4061, 1997. 18. De Smidt O, Albertyn J, Bragg RR, Van Heerden E. Genetic organisation of the capsule transport gene region from Haemophilus paragallinarum. The Onderstepoort Journal of Veterinary Research. 71:139-152, 2004. 19. Delaplane JP, Erwin LE, Stuart HO. Hemophilic bacillus as the cause of an infectious rhinitis. 244:1-12, 1934. 20. Droual R, Bickford AA, Charlton BR, Cooper GL, Channing SE. Infectious coryza in meat chickens in the San Joaquin Valley of California. Avian Diseases. 34:1009-1016, 1990. 21. Eaves LE, Rogers DG, Blackall PJ. Comparison of hemagglutinin and agglutinin schemes for the serological classification of Haemophilus paragallinarum and proposal of a new hemagglutinin serovar. Journal of Clinical Microbiology. 27:1510-1513, 1989. 22. Elliot CP, MR. L. A hemophilic bacterium as a cause of infectious coryza in the fowl. J Am Vet Med Assoc 37: 877-888, 1934. 23. Elwell CA, Dreyfus LA. DNase I homologous residues in CdtB are critical for cytolethal distending toxin-mediated cell cycle arrest. Molecular Microbiology. 37:952-963, 2000. 24. Gulig PA, Patrick CC, Hermanstorfer L, McCracken GH, Jr., Hansen EJ. Conservation of epitopes in the oligosaccharide portion of the lipooligosaccharide of Haemophilus influenzae type b. Infect Immun. 55:513-520, 1987. 25. Hinz KH. [Report on the differentiation of Haemophilus isolates from chickens. I. Note: cultural and biochemical studies]. Avian Pathology: Journal of the WVPA. 2:211-229, 1973. 26. Hobb RI, Tseng HJ, Downes JE, Terry TD, Blackall PJ, Takagi M, Jennings MP. Molecular analysis of a haemagglutinin of Haemophilus paragallinarum. Microbiology. 148:2171-2179, 2002. 27. Hsu YM, Shieh HK, Chen WH, Shiang JH, Chang PC. Immunogenicity and haemagglutination of recombinant Avibacterium paragallinarum HagA. Vet Microbiol. 122:280-289, 2007. 28. Hsu YM, Shieh HK, Chen WH, Sun TY, Shiang JH. Antimicrobial susceptibility, plasmid profiles and haemocin activities of Avibacterium paragallinarum strains. Vet Microbiol. 124:209-218, 2007. 29. Inzana TJ, Hensley J, McQuiston J, Lesse AJ, Campagnari AA, Boyle SM, Apicella MA. Phase variation and conservation of lipooligosaccharide epitopes in Haemophilus somnus. Infect Immun. 65:4675-4681, 1997. 30. Iritani Y, Iwaki S, Yamaguchi T. Biological activities of crude polysaccharide extracted from two different immunotype strains of Hemophilus gallinarum in chickens. Avian Dis. 25:29-37, 1981. 31. Jacobs AA, Cuenen W, Storm PK. Efficacy of a trivalent Haemophilus paragallinarum vaccine compared to bivalent vaccines. Vet Microbiol. 32:43-49, 1992. 32. Jacobs AA, van den Berg K, Malo A. Efficacy of a new tetravalent coryza vaccine against emerging variant type B strains. Avian Pathol. 32:265-269, 2003. 33. Jessing SG, Ahrens P, Inzana TJ, Angen O. The genetic organisation of the capsule biosynthesis region of Actinobacillus pleuropneumoniae serotypes 1, 6, 7, and 12. Vet Microbiol. 129:350-359, 2008. 34. Johnson WM, Lior H. A new heat-labile cytolethal distending toxin (CLDT) produced by Escherichia coli isolates from clinical material. Microb Pathog. 4:103-113, 1988. 35. Johnson WM, Lior H. A new heat-labile cytolethal distending toxin (CLDT) produced by Campylobacter spp. Microb Pathog. 4:115-126, 1988. 36. Johnson WM, Lior H. A new heat-labile cytolethal distending toxin (CLDT) produced by Campylobacter spp. Microb Pathog. 4:115-126, 1988. 37. Kristensen BM, Frees D, Bojesen AM. GtxA from Gallibacterium anatis, a cytolytic RTX-toxin with a novel domain organisation. Vet Res. 41:25, 2010. 38. Kroll JS, Loynds BM, Moxon ER. The Haemophilus influenzae capsulation gene cluster: a compound transposon. Mol Microbiol. 5:1549-1560, 1991. 39. Kume K, Sawata A, Nakai T. Serologic and immunologic studies on three types of hemagglutinin of Haemophilus paragallinarum serotype 1 organisms. Nihon Juigaku Zasshi The Japanese Journal of Veterinary Science. 45:783-792, 1983. 40. Kume K, Sawata A, Nakai T, Matsumoto M. Serological classification of Haemophilus paragallinarum with a hemagglutinin system. Journal of Clinical Microbiology. 17:958-964, 1983. 41. Liyanage NPM, Dassanayake RP, Kuszynski CA, Duhamel GE. Contribution of Helicobacter hepaticus cytolethal distending toxin subunits to human epithelial cell cycle arrest and apoptotic death in vitro. Helicobacter. 18:433-443, 2013. 42. Mayer MP, Bueno LC, Hansen EJ, DiRienzo JM. Identification of a cytolethal distending toxin gene locus and features of a virulence-associated region in Actinobacillus actinomycetemcomitans. Infect Immun. 67:1227-1237, 1999. 43. Mena-Rojas E, Vazquez Cruz C, Vaca Pacheco S, Garcia Gonzalez O, Perez-Marquez VM, Perez-Mendez A, Ibarra-Caballero J, de la Garza M, Zenteno E, Negrete-Abascal E. Antigenic secreted proteins from Haemophilus paragallinarum. A 110-kDa putative RTX protein. FEMS Microbiol Lett. 232:83-87, 2004. 44. Miflin JK, Chen X, Blackall PJ. Molecular characterization of isolates of Haemophilus paragallinarum from China by ribotyping. Avian Pathology: Journal of the WVPA. 26:119-127, 1997. 45. Miflin JK, Chen X, Blackall PJ. Molecular characterization of isolates of Haemophilus paragallinarum from China by ribotyping. Avian Pathol. 26:119-127,1997. 46. Mortensen NP, Schiellerup P, Boisen N, Klein BM, Locht H, Abuoun M, Newell D, Krogfelt KA. The role of Campylobacter jejuni cytolethal distending toxin in gastroenteritis: toxin detection, antibody production, and clinical outcome. APMIS. 119:626-634, 2011. 47. Mouahid M BK, and Zouagui Z. . Preparation and use of an autogenous bacterin against infectious coryza in chickens. Vet Res Commun. 15:413-419, 1991. 48. Moxon ER, Kroll JS: The Role of Bacterial Polysaccharide Capsules as Virulence Factors, in Jann PDK, Jann DB (eds): Bacterial Capsules, Vol Springer Berlin Heidelberg, 1990, pp 65-85. 49. Nakajima T, Hirayama J, Tazumi A, Hayashi K, Tasaki E, Asakura M, Yamasaki S, Moore JE, Millar BC, Matsuda M. Comparative analysis of Campylobacter lari cytolethal distending toxin (CDT) effect on HeLa cells. J Basic Microbiol. 52:559-565, 2012. 50. Noro T, Oishi E, Kaneshige T, Yaguchi K, Amimoto K, Shimizu M. Identification and characterization of haemagglutinin epitopes of Avibacterium paragallinarum serovar C. Veterinary Microbiology. 131:406-413, 2008. 51. Noro T, Yaguchi K, Amimoto K, Oishi E. Identification and expression of a gene encoding an epitope that induces hemagglutination inhibition antibody to Avibacterium paragallinarum serovar A. Avian Diseases. 51:84-89, 2007. 52. Ogunnariwo JA, Schryvers AB. Correlation between the ability of Haemophilus paragallinarum to acquire ovotransferrin-bound iron and the expression of ovotransferrin-specific receptors. Avian Dis. 36:655-663, 1992. 53. Okuda J, Fukumoto M, Takeda Y, Nishibuchi M. Examination of diarrheagenicity of cytolethal distending toxin: suckling mouse response to the products of the cdtABC genes of Shigella dysenteriae. Infect Immun. 65:428-433, 1997. 54. Page LA. Haemophilus infections in chickens. I. Characteristics of 12 Haemophilus isolates recovered from diseased chickens. American Journal of Veterinary Research. 23:85-95, 1962. 55. Page LA, Rosenwald AS, Price FC. Haemophilus infections in chickens. IV. Results of laboratory and fieldtrials of formalinized bacterins for the prevention of disease caused by Haemophilus gallinarum. Avian Dis. 7:239-256, 1963. 56. Pan YC, Tan DH, Shien JH, Liu CC, He YS, Shen PC, Chang PC. Identification and characterization of an RTX toxin-like gene and its operon from Avibacterium paragallinarum. Avian Dis. 56:537-544, 2012. 57. Pérès SY, Marchès O, Daigle F, Nougayrède JP, Herault F, Tasca C, De Rycke J, Oswald E. A new cytolethal distending toxin (CDT) from Escherichia coli producing CNF2 blocks HeLa cell division in G2/M phase. Molecular Microbiology. 24:1095-1107, 1997. 58. Pickett CL, Cottle DL, Pesci EC, Bikah G. Cloning, sequencing, and expression of the Escherichia coli cytolethal distending toxin genes. Infect Immun. 62:1046-1051, 1994. 59. Piechulla K, Hinz KH, Mannheim W. Genetic and phenotypic comparison of three new avian Haemophilus-like taxa and of Haemophilus paragallinarum Biberstein and White 1969 with other members of the family Pasteurellaceae Pohl 1981. Avian Diseases. 29:601-612, 1985. 60. Quinn PJ, Markey BK, Leonard FC, FitzPatrick ES, Fanning S, Hartigan P: Veterinary Microbiology and Microbial Disease, John Wiley & Sons, 2011. 61. Reid GG, Blackall PJ. Comparison of adjuvants for an inactivated infectious coryza vaccine. Avian Dis. 31:59-63, 1987. 62. Rivero-Garcia PC, Cruz CV, Alonso PS, Vaca S, Negrete-Abascal E. Haemophilus paragallinarum secretes metalloproteases. Can J Microbiol. 51:893-896, 2005. 63. Roberts IS. The biochemistry and genetics of capsular polysaccharide production in bacteria. Annu Rev Microbiol. 50:285-315, 1996. 64. Sandoval VE, Terzolo HR, Blackall PJ. Complicated infectious coryza outbreaks in Argentina. Avian Diseases. 38:672-678, 1994. 65. Satola SW, Schirmer PL, Farley MM. Complete sequence of the cap locus of Haemophilus influenzae serotype b and nonencapsulated b capsule-negative variants. Infect Immun. 71:3639-3644, 2003. 66. Sawata A, Kume K, Nakai T. Susceptibility of Haemophilus paragallinarum to bactericidal activity of normal and immune chicken sera. Nihon Juigaku Zasshi The Japanese Journal of Veterinary Science. 46:805-813, 1984. 67. Sawata A, Kume K, Nakase Y. Antigenic structure and relationship between serotypes 1 and 2 of Haemophilus paragallinarum. American Journal of Veterinary Research. 40:1450-1453, 1979. 68. Sawata A, Kume K, Nakase Y. Biologic and serologic relationships between Page's and Sawata's serotypes of Haemophilus paragallinarum. American Journal of Veterinary Research. 41:1901-1904, 1980. 69. Sawata A, Kume K, Nakase Y. Hemagglutinin of Haemophilus paragallinarum serotype 2 organisms: occurrence and immunologic properties of hemagglutinin. American Journal of Veterinary Research. 43:1311-1314, 1982. 70. Sawata A, Nakai T, Kume K, Yoshikawa H, Yoshikawa T. Intranasal inoculation of chickens with encapsulated or nonencapsulated variants of Haemophilus paragallinarum: electron microscopic evaluation of the nasal mucosa. American Journal of Veterinary Research. 46:2346-2353, 1985. 71. Sawata A, Nakai T, Kume K, Yoshikawa H, Yoshikawa T. Lesions induced in the respiratory tract of chickens by encapsulated or nonencapsulated variants of Haemophilus paragallinarum. American Journal of Veterinary Research. 46:1185-1191, 1985. 72. Smith AN, Boulnois GJ, Roberts IS. Molecular analysis of the Escherichia coli K5 kps locus: identification and characterization of an inner-membrane capsular polysaccharide transport system. Molecular Microbiology. 4:1863-1869, 1990. 73. Svab D, Horvath B, Maroti G, Dobrindt U, Toth I. Sequence variability of P2-like prophage genomes carrying the cytolethal distending toxin V operon in Escherichia coli O157. Appl Environ Microbiol. 79:4958-4964, 2013. 74. Takagi M, Hirayama N, Makie H, Ohta S. Production, characterization and protective effect of monoclonal antibodies to Haemophilus paragallinarum serotype A. Vet Microbiol. 27:327-338, 1991. 75. Terzolo HR, Paolicchi FA, Sandoval VE, Blackall PJ, Yamaguchi T, Iritani Y. Characterization of isolates of Haemophilus paragallinarum from Argentina. Avian Diseases. 37:310-314, 1993. 76. Terzolo HR, Sandoval VE, Pondal FG. Evaluation of inactivated infectious coryza vaccines in chickens challenged by serovar B strains of Haemophilus paragallinarum. Avian Pathol. 26:365-376, 1997. 77. Thitisak W, Janviriyasopak O, Morris RS, Srihakim S, van Kruedener R. Causes of death found in an epidemiological study of native chickens in Thai villages. Acta Veterinaria Scandinavica Supplementum. 84:200-202, 1988. 78. Townsend KM, Boyce JD, Chung JY, Frost AJ, Adler B. Genetic organization of Pasteurella multocida cap Loci and development of a multiplex capsular PCR typing system. J Clin Microbiol. 39:924-929, 2001. 79. Tzu-Yi Tu AM-KH, A Duen-Huey Tan,A Shan-Chia Ou,A Jui-Hung Shien,B Ting-Ying Yen,A and Poa-Chun ChangACD. Loss of the Capsule Increases the Adherence Activity but Decreases the Virulence of Avibacterium paragallinarum. AVIAN DISEASES 59:87-93, 2015. 80. Ueda S, Nagasawa Y, Suzuki T, Tajima M. Adhesion of Haemophilus paragallinarum to cultured chicken cells. Microbiology and Immunology. 26:1007-1016, 1982. 81. Vertieva E, Kobozev M, Tartakovskaya D, Araslanova V, Belyi Y. Genetic constructions, hyperexpressing recombinant fragments of cytolethal distending toxin of Aggregatibacter actinomycetemcomitans. World Journal of Microbiology and Biotechnology. 27:1189-1196, 2010. 82. Wang X, Li L, Yang M, Geng Y, Chen H, Xu Y, Sun Y. Prevalence and distribution of Aggregatibacter actinomycetemcomitans and its cdtB gene in subgingival plaque of Chinese periodontitis patients. BMC Oral Health. 14:37, 2014. 83. Wu J-R, Wu Y-R, Shien J-H, Hsu Y-M, Chen C-F, Shieh HK, Chang P-C. Recombinant proteins containing the hypervariable region of the haemagglutinin protect chickens against challenge with Avibacterium paragallinarum. Vaccine. 29:660-667, 2011. 84. Wu JR, Chen PY, Shien JH, Shyu CL, Shieh HK, Chang F, Chang PC. Analysis of the biosynthesis genes and chemical components of the capsule of Avibacterium paragallinarum. Vet Microbiol. 145:90-99, 2010. 85. Yamaguchi T, Iritani Y, Hayashi Y. Hemagglutinating activity and immunological properties of Haemophilus paragallinarum field isolates in Japan. Avian Diseases. 33:511-515, 1989. 86. Yamaguchi T, Kobayashi M, Masaki S, Iritani Y. Isolation and characterization of a Haemophilus paragallinarum mutant that lacks a hemagglutinating antigen. Avian Diseases. 37:970-976, 1993. 87. Young VB, Knox KA, Schauer DB. Cytolethal distending toxin sequence and activity in the enterohepatic pathogen Helicobacter hepaticus. Infect Immun. 68:184-191, 2000. 88. Zhang B, He Y, Xu C, Xu L, Feng S, Liao M, Ren T. Cytolethal distending toxin (CDT) of the Haemophilus parasuis SC096 strain contributes to serum resistance and adherence to and invasion of PK-15 and PUVEC cells. Veterinary Microbiology. 157:237-242, 2012. 
摘要: Infectious coryza (IC), caused by Avibacterium paragallinarum, is an important respiratory disease of chicken that may lead to growth retardation and reduced egg production. The disease causes substantial economic losses in many countries of the world. Av. paragallinarum is a Gram-negative, facultatively anaerobic, rod shaped bacteria in the family of Pasteurellaceae. Cytolethal distending toxin (CDT) is a highly conserved exotoxin produced by a number of Gram-negative bacteria. CDT kills the host cells by inhibiting cell division and causing apoptosis. In this study, CDT-deficient mutants derived from strains TW94 and TW07 of Av. paragallinarum were constructed by using the TargeTron gene knockout system. The CDT-deficient mutants were characterized to investigate the role that CDT may play in the virulence of Av. paragallinarum. Further, recombinant CDT proteins were produced and used a vaccine antigen against Av. paragallinarum. The result showed that recombinant CDT proteins have potential to be used as vaccine antigens against Av. paragallinarum.
雞傳染性鼻炎菌 (Avibacterium paragallinarum, Av. paragallinarum) 為引起雞傳染性可利查 (Infectious coryza, IC) 之病原菌,此病又可稱作 雞傳染性鼻炎,為雞隻重要的上呼吸道感染疾病,可造成肉雞體重下降 淘汰率增加及蛋雞產蛋率下降,造成全球經濟嚴重的損失。雞傳染性鼻 炎菌為格蘭氏陰性菌細菌、兼性厭氧、桿狀型態的巴氏德桿菌家族,細 胞致死腫脹毒素 (CDT) 是許多革蘭氏陰性細菌的重要毒素蛋白,所產 生的高度保留外毒素因子,會影響宿主細胞分裂停滯進而走向凋亡。在 本研究中,在雞傳染性鼻炎菌的 TW07 及 TW94 菌株中使用商業套組 TargeTron 使 CdtB 基因不活化成為 CDT 基因缺損株,比較野生株與 突變株之差異,探討在雞傳染性鼻炎菌的毒力因子中扮演重要的角色, 另外利用表現重組蛋白技術表現出 CDT 重組蛋白,進而針對雞傳染性 鼻炎菌發展次單位疫苗。本研究結果發現 CDT 基因缺損株之毒素被破 壞後,對於細胞腫脹的程度明顯的減少,另一方面動物實驗結果發現, CDT 重組蛋白,可作為雞傳染性鼻炎菌之疫苗抗原。 
URI: http://hdl.handle.net/11455/93095
文章公開時間: 10000-01-01
Appears in Collections:微生物暨公共衛生學研究所

文件中的檔案:

取得全文請前往華藝線上圖書館



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.