請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77802
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 王錦堂 | zh_TW |
dc.contributor.advisor | Jin-Town Wang | en |
dc.contributor.author | 柯彥溥 | zh_TW |
dc.contributor.author | Yen-Pu Ko | en |
dc.date.accessioned | 2021-07-11T14:35:07Z | - |
dc.date.available | 2024-02-28 | - |
dc.date.copyright | 2018-10-11 | - |
dc.date.issued | 2018 | - |
dc.date.submitted | 2002-01-01 | - |
dc.identifier.citation | 1. Podschun R, Ullmann U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clinical microbiology reviews. 1998;11(4):589-603.
2. Siu LK, Yeh KM, Lin JC, Fung CP, Chang FY. Klebsiella pneumoniae liver abscess: a new invasive syndrome. The Lancet infectious diseases. 2012;12(11):881-887. 3. Fung CP, Chang FY, Lee SC, et al. A global emerging disease of Klebsiella pneumoniae liver abscess: is serotype K1 an important factor for complicated endophthalmitis? Gut. 2002;50(3):420-424. 4. Wang JH, Liu YC, Lee SS, et al. Primary liver abscess due to Klebsiella pneumoniae in Taiwan. Clinical infectious diseases. 1998;26(6):1434-1438. 5. Cheng HP, Chang FY, Fung CP, Siu LK. Klebsiella pneumoniae liver abscess in Taiwan is not caused by a clonal spread strain. Journal of microbiology, immunology, and infection. 2002;35(2):85-88. 6. Paczosa MK, Mecsas J. Klebsiella pneumoniae: Going on the offense with a strong defense. Microbiology and molecular biology reviews. 2016;80(3):629-661. 7. ECDC. Healthcare-associated infections acquired in intensive care units(2015). 8. CDC. https://www.cdc.gov/hai/surveillance/data-reports/2015-SIR-report.html. 9. TCDC. Annual report of nosocomial infections surveillance system (2015). 10. Roberts IS. The biochemistry and genetics of capsular polysaccharide production in bacteria. Annual review of microbiology. 1996;50:285-315. 11. Bradford PA. Extended-spectrum beta-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clinical microbiology reviews. 2001;14(4):933-951. 12. Knothe H, Shah P, Krcmery V, Antal M, Mitsuhashi S. Transferable resistance to cefotaxime, cefoxitin, cefamandole and cefuroxime in clinical isolates of Klebsiella pneumoniae and Serratia marcescens. Infection. 1983;11(6):315-317. 13. Jan IS, Hsueh PR, Teng LJ, Ho SW, Luh KT. Antimicrobial susceptibility testing for Klebsiella pneumoniae isolates resistant to extended-spectrum beta-lactam antibiotics. Journal of the Formosan medical association. 1998;97(10):661-666. 14. Yagi T, Kurokawa H, Shibata N, Shibayama K, Arakawa Y. A preliminary survey of extended-spectrum beta-lactamases (ESBLs) in clinical isolates of Klebsiella pneumoniae and Escherichia coli in Japan. FEMS microbiology letters. 2000;184(1):53-56. 15. Martins-Loureiro M, de Moraes BA, de Mendonca VL, Rocha-Quadra MR, dos Santos-Pinheiro G, Dutra-Asensi M. Molecular epidemiology of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae isolated from neonatal intensive care unit patients involved in hospital infection cases in Rio de Janeiro, Brazil. Revista latinoamericana de microbiologia. 2001;43(2):88-95. 16. Edelstein M, Pimkin M, Palagin I, Edelstein I, Stratchounski L. Prevalence and molecular epidemiology of CTX-M extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Russian hospitals. Antimicrobial agents and chemotherapy. 2003;47(12):3724-3732. 17. Bagattini M, Crivaro V, Di Popolo A, et al. Molecular epidemiology of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a neonatal intensive care unit. The Journal of antimicrobial chemotherapy. 2006;57(5):979-982. 18. Yigit H, Queenan AM, Anderson GJ, et al. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrobial agents and chemotherapy. 2001;45(4):1151-1161. 19. Hsueh PR, Liu CY, Luh KT. Current status of antimicrobial resistance in Taiwan. Emerging infectious diseases. 2002;8(2):132-137. 20. Patel G, Huprikar S, Factor SH, Jenkins SG, Calfee DP. Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infection control and hospital epidemiology. 2008;29(12):1099-1106. 21. Bratu S, Landman D, Haag R, et al. Rapid spread of carbapenem-resistant Klebsiella pneumoniae in New York City: a new threat to our antibiotic armamentarium. Archives of internal medicine. 2005;165(12):1430-1435. 22. Leavitt A, Navon-Venezia S, Chmelnitsky I, Schwaber MJ, Carmeli Y. Emergence of KPC-2 and KPC-3 in carbapenem-resistant Klebsiella pneumoniae strains in an Israeli hospital. Antimicrobial agents and chemotherapy. 2007;51(8):3026-3029. 23. Ahmad TA, El-Sayed LH, Haroun M, Hussein AA, El Ashry el SH. Development of immunization trials against Klebsiella pneumoniae. Vaccine. 2012;30(14):2411-2420. 24. Green JH, Pigott NE, Bolin RC, Harrell WK. Use of acetone-dried vaccines for preparing capsular antisera against the Klebsiella group and the lyophilization of Klebsiella cultures. Applied microbiology. 1970;20(3):416-420. 25. Kuenen JD, van Dijke EE, Hol C, Bootsma HJ, Verhoef J, van Dijk H. Protective effects of orally administered, Klebsiella-containing bacterial lysates in mice. FEMS immunology and medical microbiology. 1994;8(1):69-75. 26. Michel FB, Dussourd D'Hinterland L, Bousquet J, Pinel AM, Normier G. Immuno-stimulation by a ribosomal vaccine associated with a bacterial cell wall adjuvant in humans. Infection and immunity. 1978;20(3):760-769. 27. Roe EA, Jones RJ. Vaccination against Klebsiella aerogenes. The Journal of hygiene. 1984;93(2):355-363. 28. Cryz SJ, Jr., Furer E, Germanier R. Immunization against fatal experimental Klebsiella pneumoniae pneumonia. Infection and immunity. 1986;54(2):403-407. 29. Cryz SJ, Jr., Mortimer P, Cross AS, Furer E, Germanier R. Safety and immunogenicity of a polyvalent Klebsiella capsular polysaccharide vaccine in humans. Vaccine. 1986;4(1):15-20. 30. Granstrom M, Wretlind B, Markman B, Cryz S. Enzyme-linked immunosorbent assay to evaluate the immunogenicity of a polyvalent Klebsiella capsular polysaccharide vaccine in humans. Journal of clinical microbiology. 1988;26(11):2257-2261. 31. Edelman R, Taylor DN, Wasserman SS, et al. Phase 1 trial of a 24-valent Klebsiella capsular polysaccharide vaccine and an eight-valent Pseudomonas O-polysaccharide conjugate vaccine administered simultaneously. Vaccine. 1994;12(14):1288-1294. 32. Pan YJ, Lin TL, Lin YT, et al. Identification of capsular types in carbapenem-resistant Klebsiella pneumoniae strains by wzc sequencing and implications for capsule depolymerase treatment. Antimicrobial agents and chemotherapy. 2015;59(2):1038-1047. 33. Hsu CR, Lin TL, Pan YJ, Hsieh PF, Wang JT. Isolation of a bacteriophage specific for a new capsular type of Klebsiella pneumoniae and characterization of its polysaccharide depolymerase. PloS one. 2013;8(8):e70092. 34. Lin KH, Liang JJ, Huang WI, et al. In vivo protection provided by a synthetic new alpha-galactosyl ceramide analog against bacterial and viral infections in murine models. Antimicrobial agents and chemotherapy. 2010;54(10):4129-4136. 35. Hung JT, Huang JR, Yu AL. Tailored design of NKT-stimulatory glycolipids for polarization of immune responses. Journal of biomedical science. 2017;24(1):22. 36. Maslanka SE, Gheesling LL, Libutti DE, et al. Standardization and a multilaboratory comparison of Neisseria meningitidis serogroup A and C serum bactericidal assays. The Multilaboratory Study Group. Clinical and diagnostic laboratory immunology. 1997;4(2):156-167. 37. Milagres LG, Gorla MC, Sacchi CT, Rodrigues MM. Specificity of bactericidal antibody response to serogroup B meningococcal strains in Brazilian children after immunization with an outer membrane vaccine. Infection and immunity. 1998;66(10):4755-4761. 38. Gioia CA, de Sousa AB, Cruz SC, et al. Effect of a booster dose of serogroup B meningococcal vaccine on antibody response to Neisseria meningitidis in mice vaccinated with different immunization schedules. FEMS immunology and medical microbiology. 2005;44(1):35-42. 39. Follador R, Heinz E, Wyres KL, et al. The diversity of Klebsiella pneumoniae surface polysaccharides. Microbial genomics. 2016;2(8):e000073. 40. Liu Y, Liu PP, Wang LH, Wei DD, Wan LG, Zhang W. Capsular polysaccharide types and virulence-related traits of epidemic KPC-producing Klebsiella pneumoniae isolates in a Chinese university hospital. Microbial drug resistance. 2017;23(7):901-907. 41. Romero-Steiner S, Libutti D, Pais LB, et al. Standardization of an opsonophagocytic assay for the measurement of functional antibody activity against Streptococcus pneumoniae using differentiated HL-60 cells. Clinical and diagnostic laboratory immunology. 1997;4(4):415-422. 42. Guttormsen HK, Liu Y, Paoletti LC. Functional activity of antisera to group B streptococcal conjugate vaccines measured with an opsonophagocytosis assay and HL-60 effector cells. Human vaccines. 2008;4(5):370-374. 43. Seeberger PH, Pereira CL, Khan N, et al. A semi-synthetic glycoconjugate vaccine candidate for carbapenem-resistant Klebsiella pneumoniae. Angewandte Chemie (International ed in English). 2017;56(45):13973-13978. | - |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77802 | - |
dc.description.abstract | 克雷伯氏肺炎桿菌(Klebsiella pneumoniae)是人類呼吸道及消化道的正常菌叢,會伺機性造成免疫不全病人之院內感染及正常人之社區型感染。多重抗藥性克雷伯氏肺炎桿菌更是造成臨床上治療病人極大的困難,利用疫苗使宿主的免疫系統產生記憶性抗體作為替代療法可能是一個不錯的方法。先前實驗室研究台大、成大、榮總及長庚四家醫院之碳青黴烯類抗生素抗藥性的克雷伯氏肺炎桿菌臨床菌株之莢膜型,其中5種莢膜型(K64、K62、K24、KN2、K28)就佔了約72%的菌株。首先,本研究成功表現並純化出K24及K28莢膜分解酵素,分別針對K24及K28菌株有良好的活性。接著利用先前實驗室所純化出的噬菌體莢膜分解酵素將細菌莢膜切割成小片段醣分子,並與易誘發免疫反應的載體蛋白質CRM197連接製成莢膜接合疫苗,評估兩個多重抗藥性菌株最常見莢膜型K62及K64之莢膜接合疫苗在BALB/c小鼠之安全性、抗體產生能力,及以cyclophosphamide建立免疫不全小鼠模式模擬疫苗是否可對臨床上免疫不全病人感染多重抗藥性克雷伯氏肺炎桿菌提供保護力。K62及K64莢膜接合疫苗安全性方面,小鼠接種疫苗18-24小時後量測肛溫及體重並無不良反應。K62莢膜接合疫苗可誘發K62莢膜抗體產生,其血清殺菌試驗約有40%(6/15)小鼠血清為陽性反應,接種四劑及五劑K62莢膜接合疫苗可顯著增加感染致死劑量之K62菌株的免疫抑制小鼠存活率。K64莢膜接合疫苗誘發抗體產生能力不佳,推測可能由於K64菌株之莢膜結構抗原性差或是接合的方法等原因所造成。 | zh_TW |
dc.description.abstract | Klebsiella pneumoniae is normal flora of human respiratory tract and digestive tract, and sometimes becomes opportunistic pathogen which causes nosocomial infection of immunocompromised patients or community-acquired infection of healthy people. Multidrug resistant K. pneumoniae(MDRKP) is a clinical urgent problem. Preventive immunization through vaccines may be an alternative treatment against MDRKP infection in prospective host. Our previous study showed that K64, K62, K24, KN2, and K28 capsular type account for 72% of carbapenem-resistant K. pneumoniae (CRKP) collected from 4 hospitals of Taiwan. In the first part of this study, K24 and K28 capsule depolymerases were successfully expressed and purified, and the enzymatic activity toward K24 and K28 strains was demonstrated, respectively. Next, we used previously purified capsule depolymerases to digest capsule into fragments, which were conjugated with high immunogenic carrier protein CRM197 to generate capsule conjugate vaccines. K62 and K64 capsule conjugate vaccines, two of the CRKP prevalent capsular type, were generated and evaluated. The safety, antibody production ability, serum bactericidal activity, and protective efficacy in cyclophosphamide-treated BALB/c mice, which mimic immunocompromised patients, were studied. 18-24 hours after immunization, no adverse effect was observed in body temperature and weight of K62 and K64 conjugate vaccine-immunized mice. K62 conjugate vaccine induced the production of K62 capsule antibody, and provoked the serum bactericidal activity in 6/15 (40%) of mice. Receiving 4 or 5 doses of K62 conjugate vaccine significantly increased the survival of immunocompromised mice when challenged with lethal dose of K62 strain. However, K64 conjugate vaccine failed to induce the production of K64 capsule antibody. We speculate low antigenicity of K64 capsular polysaccharide structure or conjugation methods might affect the immunogenicity of K64 capsule conjugate vaccine. | en |
dc.description.provenance | Made available in DSpace on 2021-07-11T14:35:07Z (GMT). No. of bitstreams: 1 ntu-107-R05445101-1.pdf: 36303293 bytes, checksum: b2034db970ad53f8b82cbb29739b1e9e (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 口試委員審定書 ............................................................................................................................... I
中文摘要 ............................................................................................................................................ II Abstract ............................................................................................................................................... III 目錄 ..................................................................................................................................................... V 圖目錄 .............................................................................................................................................. VII 表目錄 ............................................................................................................................................. VIII 第一章、緒論 .................................................................................................................................. 1 1. 克雷伯氏肺炎桿菌基本介紹 ................................................................................................ 1 2. 先前研發之克雷伯氏肺炎桿菌疫苗 ................................................................................. 2 3. 多重抗藥性克雷伯氏肺炎桿菌莢膜接合疫苗 .............................................................. 2 4. 研究目的 ....................................................................................................................................... 3 第二章、材料與方法 .................................................................................................................... 4 1. 實驗菌株 ....................................................................................................................................... 4 2. 實驗噬菌體 .................................................................................................................................. 4 3. K24dep及K28dep基因選殖(Cloning) ................................................................................ 4 4. 蛋白質純化及表現 ................................................................................................................... 5 5. 塗點試驗(Spot test) .................................................................................................................... 7 6. SDS膠體電泳與考馬思亮藍(Coomassie brilliant blue)蛋白質定量法 ................ 7 7. 實驗動物 ....................................................................................................................................... 8 8. 疫苗與接種方法與接種時程 ................................................................................................ 9 9. 免疫斑點試驗(Dot blot) ............................................................................................................ 9 10. 血清殺菌試驗 ........................................................................................................................ 9 11. 免疫不全小鼠模式及致死劑量感染試驗 ................................................................... 10 第三章、結果 ............................................................................................................. 11 1. 表現及純化克雷伯氏肺炎桿菌K24及K28之莢膜分解酵素 .......................... 11 2. 莢膜接合疫苗合成與接種 .................................................................................. 11 3. K62及K64 莢膜接合疫苗保護力 ..................................................................................... 12 3-1. K62及K64莢膜接合疫苗之安全性 ............................................................................. 12 3-2. K62及K64莢膜接合疫苗之抗體產生能力 ............................................................... 12 3-3. 血清殺菌試驗 ...................................................................................................................... 13 3-4. 致死劑量K62菌株感染來測試K62莢膜接合疫苗對免疫不全小鼠之保護力 ................................................................................................................................................................ 13 第四章、討論 ........................................................................................................... 14 參考文獻 ................................................................................................................... 29 附錄 ........................................................................................................................... 34 | - |
dc.language.iso | zh_TW | - |
dc.title | 多重抗藥性K62及K64克雷伯氏肺炎桿菌莢膜接合疫苗在免疫功能不全小鼠模式之效用評估 | zh_TW |
dc.title | Efficacy of K62 and K64 Capsule Conjugate Vaccines of Multidrug Resistant Klebsiella pneumoniae in Immunocompromised Mice | en |
dc.type | Thesis | - |
dc.date.schoolyear | 106-2 | - |
dc.description.degree | 碩士 | - |
dc.contributor.oralexamcommittee | 吳世雄;伍安怡;吳宗益 | zh_TW |
dc.contributor.oralexamcommittee | ;; | en |
dc.subject.keyword | 克雷伯氏肺炎桿菌,多重抗藥性,莢膜分解酵素,莢膜接合疫苗, | zh_TW |
dc.subject.keyword | Klebsiella pneumoniae,multidrug resistant,capsule depolymerase,capsule conjugate vaccine, | en |
dc.relation.page | 34 | - |
dc.identifier.doi | 10.6342/NTU201801354 | - |
dc.rights.note | 未授權 | - |
dc.date.accepted | 2018-07-11 | - |
dc.contributor.author-college | 醫學院 | - |
dc.contributor.author-dept | 微生物學研究所 | - |
dc.date.embargo-lift | 2023-10-11 | - |
顯示於系所單位: | 微生物學科所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-106-2.pdf 目前未授權公開取用 | 35.45 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。