請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18302完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 方啟泰(Chi-Tai Fang) | |
| dc.contributor.author | Wen-Chi Hsieh | en |
| dc.contributor.author | 謝汶娸 | zh_TW |
| dc.date.accessioned | 2021-06-08T00:58:50Z | - |
| dc.date.copyright | 2015-03-12 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2015-01-27 | |
| dc.identifier.citation | 1. Rahimian J, Wilson T, Oram V, Holzman RS (2004) Pyogenic liver abscess: recent trends in etiology and mortality. Clin Infect Dis 39: 1654-1659. 2. Fang CT, Chuang YP, Shun CT, Chang SC, Wang JT (2004) A novel virulence gene in Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications. J Exp Med 199: 697-705. 3. Cheng NC, Yu YC, Tai HC, Hsueh PR, Chang SC, et al. (2012) Recent trend of necrotizing fasciitis in Taiwan: focus on monomicrobial Klebsiella pneumoniae necrotizing fasciitis. Clin Infect Dis 55: 930-939. 4. Lin YT, Siu LK, Lin JC, Chen TL, Tseng CP, et al. (2012) Seroepidemiology of Klebsiella pneumoniae colonizing the intestinal tract of healthy Chinese and overseas Chinese adults in Asian countries. BMC Microbiol 12: 13. 5. Smith GW, Blackwell CC, Nuki G (1997) Faecal flora in spondyloarthropathy. Br J Rheumatol 36: 850-854. 6. Hsieh PF, Lin TL, Lee CZ, Tsai SF, Wang JT (2008) Serum-induced iron-acquisition systems and TonB contribute to virulence in Klebsiella pneumoniae causing primary pyogenic liver abscess. J Infect Dis 197: 1717-1727. 7. Wang JH (1998) Primary Liver Abscess Due to Klebsiella pneumoniae in Taiwan. Clinical Infectious Diseases 26: 1434-1438. 8. Shon AS, Bajwa RP, Russo TA (2013) Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: a new and dangerous breed. Virulence 4: 107-118. 9. Tsai FC, Huang YT, Chang LY, Wang JT (2008) Pyogenic liver abscess as endemic disease, Taiwan. Emerg Infect Dis 14: 1592-1600. 10. Ali AH, Smalligan RD, Ahmed M, Khasawneh FA (2013) Pyogenic liver abscess and the emergence of Klebsiella as an etiology: a retrospective study. Int J Gen Med 7: 37-42. 11. Moore R, O'Shea D, Geoghegan T, Mallon PW, Sheehan G (2013) Community-acquired Klebsiella pneumoniae liver abscess: an emerging infection in Ireland and Europe. Infection 41: 681-686. 12. Anstey JR, Fazio TN, Gordon DL, Hogg G, Jenney AW, et al. (2010) Community-acquired Klebsiella pneumoniae liver abscesses - an 'emerging disease' in Australia. Med J Aust 193: 543-545. 13. Song YG, Shim SG, Kim KM, Lee DH, Kim DS, et al. (2014) Profiling of the bacteria responsible for pyogenic liver abscess by 16S rRNA gene pyrosequencing. J Microbiol 52: 504-509. 14. Fang CT, Lai SY, Yi WC, Hsueh PR, Liu KL, et al. (2007) Klebsiella pneumoniae genotype K1: an emerging pathogen that causes septic ocular or central nervous system complications from pyogenic liver abscess. Clin Infect Dis 45: 284-293. 15. Ma LC, Fang CT, Lee CZ, Shun CT, Wang JT (2005) Genomic heterogeneity in Klebsiella pneumoniae strains is associated with primary pyogenic liver abscess and metastatic infection. J Infect Dis 192: 117-128. 16. Hsieh PF, Lin TL, Yang FL, Wu MC, Pan YJ, et al. (2012) Lipopolysaccharide O1 antigen contributes to the virulence in Klebsiella pneumoniae causing pyogenic liver abscess. PLoS One 7: e33155. 17. March C, Cano V, Moranta D, Llobet E, Perez-Gutierrez C, et al. (2013) Role of bacterial surface structures on the interaction of Klebsiella pneumoniae with phagocytes. PLoS One 8: e56847. 18. Nassif X, Fournier JM, Arondel J, Sansonetti PJ (1989) Mucoid phenotype of Klebsiella pneumoniae is a plasmid-encoded virulence factor. Infect Immun 57: 546-552. 19. Pan YJ, Lin TL, Hsu CR, Wang JT (2011) Use of a Dictyostelium model for isolation of genetic loci associated with phagocytosis and virulence in Klebsiella pneumoniae. Infect Immun 79: 997-1006. 20. Chuang YP, Fang CT, Lai SY, Chang SC, Wang JT (2006) Genetic determinants of capsular serotype K1 of Klebsiella pneumoniae causing primary pyogenic liver abscess. J Infect Dis 193: 645-654. 21. Fung CP (2002) A global emerging disease of Klebsiella pneumoniae liver abscess: is serotype K1 an important factor for complicated endophthalmitis? Gut 50: 420–424. 22. Lin TL, Lee CZ, Hsieh PF, Tsai SF, Wang JT (2008) Characterization of integrative and conjugative element ICEKp1-associated genomic heterogeneity in a Klebsiella pneumoniae strain isolated from a primary liver abscess. J Bacteriol 190: 515-526. 23. Wu KM, Li LH, Yan JJ, Tsao N, Liao TL, et al. (2009) Genome sequencing and comparative analysis of Klebsiella pneumoniae NTUH-K2044, a strain causing liver abscess and meningitis. J Bacteriol 191: 4492-4501. 24. PODSCHUN R (1998) Klebsiella spp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors. Clin Microb Rev 11: p. 589–603. 25. Regue M, Izquierdo L, Fresno S, Pique N, Corsaro MM, et al. (2005) A second outer-core region in Klebsiella pneumoniae lipopolysaccharide. J Bacteriol 187: 4198-4206. 26. Hsu CR, Lin TL, Chen YC, Chou HC, Wang JT (2011) The role of Klebsiella pneumoniae rmpA in capsular polysaccharide synthesis and virulence revisited. Microbiology 157: 3446-3457. 27. Lai YC, Peng HL, Chang HY (2003) RmpA2, an activator of capsule biosynthesis in Klebsiella pneumoniae CG43, regulates K2 cps gene expression at the transcriptional level. J Bacteriol 185: 788-800. 28. Cheng HY, Chen YS, Wu CY, Chang HY, Lai YC, et al. (2010) RmpA regulation of capsular polysaccharide biosynthesis in Klebsiella pneumoniae CG43. J Bacteriol 192: 3144-3158. 29. XAVIER NASSIF J-MF, JOSETTE ARONDEL, AND PHILIPPE J. SANSONETTI (1989) Mucoid Phenotype of Klebsiella pneumoniae Is a Plasmid-Encoded Virulence Factors. Infection and Immunity 57: 546-552. 30. Arakawa Y, Ohta M, Wacharotayankun R, Mori M, Kido N, et al. (1991) Biosynthesis of Klebsiella K2 capsular polysaccharide in Escherichia coli HB101 requires the functions of rmpA and the chromosomal cps gene cluster of the virulent strain Klebsiella pneumoniae Chedid (O1:K2). Infect Immun 59: 2043-2050. 31. Wacharotayankun R, Arakawa Y, Ohta M, Tanaka K, Akashi T, et al. (1993) Enhancement of extracapsular polysaccharide synthesis in Klebsiella pneumoniae by RmpA2, which shows homology to NtrC and FixJ. Infect Immun 61: 3164-3174. 32. Regue M, Climent N, Abitiu N, Coderch N, Merino S, et al. (2001) Genetic characterization of the Klebsiella pneumoniae waa gene cluster, involved in core lipopolysaccharide biosynthesis. J Bacteriol 183: 3564-3573. 33. American Diabetes A (2014) Diagnosis and classification of diabetes mellitus. Diabetes Care 37 Suppl 1: S81-90. 34. Lee WC (2013) Assessing causal mechanistic interactions: a peril ratio index of synergy based on multiplicativity. PLoS One 8: e67424. 35. Brisse S, Fevre C, Passet V, Issenhuth-Jeanjean S, Tournebize R, et al. (2009) Virulent clones of Klebsiella pneumoniae: identification and evolutionary scenario based on genomic and phenotypic characterization. PLoS One 4: e4982. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18302 | - |
| dc.description.abstract | 背景 摘要 克雷伯氏肺炎桿菌 (Klebsiella pneumoniae) 肝膿瘍 (pyogenic liver abscess, PLA) 是台灣重要的社區感染症。K. pneumoniae PLA 致病機轉研究有兩個層面, 一為細菌毒力因子,另一則是宿主潛伏疾患。目前已知克雷伯氏肺炎桿菌的毒力 因子包括:莢膜 (CPS) 與脂多醣 (LPS)(有多種基因型)、胞外多醣合成轉錄促 進因子 (rmpA/A2) 和捕鐵系統 (iron-acquisition system)—Kfu 與 Yersiniabactin 位 於細菌染色體上;Aerobactin 與 Salmochelin 則位於細菌大型毒力質體 pVLP。先前 研究也發現糖尿病、肝膽疾病以及惡性腫瘤等宿主疾患是不分菌種 PLA 的危險因 子。然而,到目前為止尚無針對 K. pneumoniae PLA 危險因子的研究,克雷伯氏肺 炎桿菌致病性相關基因型在 K. pneumoniae PLA 的角色目前仍不清楚,且細菌毒力 因子與宿主疾患之間是否在 K. pneumoniae PLA 致病機轉中有協同作用也尚待釐清。 研究目的 本研究目的為分析克雷伯氏肺炎桿菌致病性相關基因型在 K. pneumoniae PLA 致病機轉所扮演的角色,並且釐清克雷伯氏肺炎桿菌致病性相關基因型與宿主疾 患在肝膿瘍致病機轉上的生物學交互作用。 方法 本研究是一以醫院為本的病例對照研究。收集 2006-2011 期間在台大醫院新診 斷的社區感染 K. pneumoniae PLA 病患作為病例組,共 90 例。將同時段內,在入 院前或入院時分離出克雷伯氏肺炎桿菌,但沒有發展為 PLA 的病患作為對照組, 共有 179 例。我們使用特異性聚合酶連鎖反應引子對從病例組與對照組分離出來 的菌株進行基因型分析,包括 CPS 和 LPS (含 OPS 與 Core 兩部分) 基因分型以及 毒力因子 rmpA/A2 和四個捕鐵系統的偵測。另一方面,查閱病患的醫療記錄,系統性地收集所有病患的基本資料以及相關病史。資料分析時使用邏輯斯迴歸分析克雷伯氏肺炎桿菌肝膿瘍的危險因子,並以 PRISM 指標檢定克雷伯氏肺炎桿菌基 因型與宿主疾患間的生物交互作用。 結果 本研究共納入 90 位病例患者以及 179 位對照患者。在病例組中,K1 (59%) 與 K2 (21%) 是最常見的兩種 CPS 基因型;O1 (93%) 與 core 1 (81%) 則是最常見的 LPS 基因型。絕大多數造成 PLA 的病例組菌株都帶有 rmpA/A2 (96%) 基因以及捕 鐵系統 kfu (64%)、irp2 (87%)、iucB (93%)、iroN (94%)。基因型 CPS、LPS 與捕鐵 系統有很強的相關性。病例組或對照組病人原本就罹患糖尿病 (47.8% vs. 55.3%) 或肝膽疾病 (38.9% vs. 45.8%) 的比例都非常高。多變項邏輯斯回歸顯示下列細菌 基因型:K1: O1: core 1: kfu+ irp2+ (adjusted OR=6.1, P<0.001)、K2: O1: core 2: irp2+ (adjusted OR=5.9, P=0.006)、pVLP: iucB+ iroN+ rmpA/A2+ (adjusted OR=8.5, P<0.001) 與 pVLP: iucB+/iroN+ (adjusted OR=6.8, P=0.028) 是造成 K. pneumoniae PLA 的獨立 危險因子,但糖尿病、肝膽疾病與惡性腫瘤等宿主疾患則不是獨立危險因子。 PRISM 檢定結果顯示基因型為 K1: O1: core 1: kfu+ irp2+ 的克雷伯氏肺炎桿菌菌株 可以在不需有糖尿病的情況下獨立造成 K. pneumoniae PLA (PRISM=0.403, P= 0.031)。然而,糖尿病可能與基因型 K2: O1: core 2: irp2+ (PRISM=2.073, P=0.470) 以 及 K2: O1: core 2: irp2− (PRISM=1.677, P=0.501) 在 K. pneumoniae PLA 的致病機轉中有協同交互作用存在。 結論 本研究證實,克雷伯氏肺炎桿菌致病性相關基因型,包括 K1: O1: core 1: kfu+ irp2+、K2: O1: core 2: irp2+、pVLP: iucB+ iroN+ rmpA/A2+ 與 pVLP: iucB+/iroN+,在 K. pneumoniae PLA 的致病機轉中扮演極重要的角色。另外,基因型為 K1: O1: core 1: kfu+ irp2+ 的克雷伯氏肺炎桿菌菌株可獨立造成 K. pneumoniae PLA 不需宿主有 糖尿病;但糖尿病與兩種 K2 基因型 K2: O1: core 2: irp2+ 與 K2: O1: core 2: irp2− 在 K. pneumoniae PLA 的致病機轉中可能有協同交互作用存在。 | zh_TW |
| dc.description.abstract | Background Klebsiella pneumoniae pyogenic liver abscess (PLA) is a community-acquired infectious disease that is endemic in Taiwan. Previous studies have suggested that both host factors and bacterial virulence factors could be involved in the pathogenesis of K. pneumoniae PLA. In K. pneumoniae, pathogenicity-associated genotypes include capsular polysaccharides (CPS), lipopolysaccharides (LPS), rmpA/A2, and iron acquisition systems: the Kfu iron acquisition system and yersiniabactin are located on the bacterial chromosome, whereas aerobactin and salmochelin are located on the large virulence plasmid pVLP. At the present time, no studies have been performed to examine the risk factors for K. pneumoniae PLA. The role of K. pneumoniae genotypes in the pathogenesis of K. pneumoniae PLA remains unclear. The pathogenesis mechanism—especially the interaction between bacterial virulence and host factors—has not yet been clarified in humans. Aims The aim of this study was to determine the role of K. pneumoniae genotypes in the pathogenesis of K. pneumoniae PLA and to determine the biological interaction of K. pneumoniae with underlying diseases in the host. Methods This is a hospital-based case-control study. New-onset community-acquired K. pneumoniae PLA cases diagnosed at National Taiwan University Hospital (NTUH) from 2006-2011 were included. The controls were patients with community-acquired K. pneumoniae isolates who did not develop PLA during the same period. We conducted PCR genotyping of CPS, LPS O antigen and core of K. pneumoniae isolates collected from cases and controls using specific primers that have been validated with WHO reference strains. We also detected the presence of rmpA/A2 and four pathogenicity islands encoding iron acquisition systems. Information on the patients’ underlying diseases was obtained by reviewing medical records. Logistic regression was used to analyze the risk factors for PLA. Further, we used the peril ratio index of synergy based on multiplicativity (PRISM) to quantify the biological interaction between KP genotypes and underlying host disease. Results A total of 90 K. pneumoniae PLA cases and 179 controls were included in this study. The most common CPS genotype among the K. pneumoniae PLA cases was K1 (59%), followed by K2 (21%). The most common LPS genotype among the cases was O1 (93%), and core 1 (81%). The majority of K. pneumoniae that caused PLA carried rmpA/A2 (96%) and the iron acquisition systems kfu (64%), irp2 (87%), iucB (93%), and iroN (94%). Diabetes mellitus and hepatobiliary disease were common in both case patients and control patients (47.8% vs. 55.3% and 38.9% vs. 45.8%, respectively). There were strong correlations among the genotypes of CPS, LPS and the presence of iron acquisition systems. Multiple logistic regression analysis showed that K1: O1: core 1: kfu+ irp2+ (adjusted OR=6.1, P<0.001), K2: O1: core 2: irp2+ (adjusted OR=5.9, P=0.006), pVLP: iucB+ iroN+ rmpA/A2+ (adjusted OR=8.5, P<0.001), and pVLP: iucB+/iroN+ (adjusted OR=6.8, P=0.028) were independent risk factors for K. pneumoniae PLA, while DM, HBD and malignancy were not independent factors. Pathogen-host interaction analysis indicated that the K. pneumoniae strains K1: O1: core 1: kfu+ irp2+ (PRISM=0.403, P=0.031) and pVLP: iucB+ iroN+ rmpA/A2+ (PRISM=0.798, P=0.176) have the potential to cause PLA independent of host DM, while DM may synergistically interact with genotypes K2: O1: core 2: irp2+ (PRISM=2.073, P=0.470) and K2: O1: core 2: irp2− (PRISM=1.677, P=0.501) in the pathogenesis of K. pneumoniae PLA. Conclusions The present study demonstrated that several K. pneumoniae genotypes including K1: O1: core 1: kfu+ irp2+, K2: O1: core 2: irp2+, pVLP: iucB+ iroN+ rmpA/A2+, and pVLP: iucB+/iroN+ play a predominant role in the pathogenesis of K. pneumoniae PLA. K. pneumoniae strains with genotypes K1: O1: core 1: kfu+ irp2+ and pVLP: iucB+ iroN+ rmpA/A2+ can cause PLA independently. DM may synergistically interact with genotypes K2: O1: core 2: irp2+ and K2: O1: core 2: irp2− in the pathogenesis of K. pneumoniae PLA. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T00:58:50Z (GMT). No. of bitstreams: 1 ntu-103-R01849023-1.pdf: 5214057 bytes, checksum: 04ffaddd42ad9b419555a1b7015f98eb (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | Contents 口試委員審定書......................................................................................... i 誌謝 ............................................................................................................. ii 摘要 ............................................................................................................ iii Abstract ...................................................................................................... vi Contents ..................................................................................................... ix List of Tables ............................................................................................ xii List of Figures .......................................................................................... xiii List of Appendices ................................................................................... xiv Chapter 1 Introduction ............................................................................1 1.1 Background....................................................................................... 1 1.2 Klebsiella pneumoniae pyogenic liver abscess ................................... 1 1.3 Pathogenesis of K. pneumoniae PLA ...................................................2 1.3.1 Host factors.....................................................................................2 1.3.2 Bacterial virulence factors ...............................................................3 (1) Capsular polysaccharides ................................................................... 3 (2) Lipopolysaccharides: O-polysaccharides (OPS) ................................... 4 (3) Lipopolysaccharides: core oligosaccharides ........................................ 4 (4) Regulator of mucoid phenotype A genes, rmpA/A2 ........................... 4 (5) Iron acquisition systems on pathogenicity island.................................. 5 1.4 Pathogen-host interaction ................................................................. 6 1.5 Unresolved questions.......................................................................... 7 1.6 Aims................................................................................................... 7 Chapter 2 Materials and Methods ..........................................................8 2.1 Study design and study samples ....................................................... 8 2.2 CPS, OPS and core genotyping .......................................................... 8 (1) Capsular polysaccharide synthesis gene cluster .................................. 9 (2) O-polysaccharide synthesis gene cluster and waa cluster of the core...........9 2.3 Detection of rmpA/A2 and PAIs ......................................................... 9 (1) Regulator of mucoid phenotype A genes ..............................................10 (2) Iron acquisition system on a pathogenicity island ................................ 10 2.4 Underlying host disease...................................................................... 10 2.5 Statistical analysis............................................................................... 10 Chapter 3 Results....................................................................................12 3.1 K, O, and core genotyping of K. pneumoniae strains........................... 12 3.2 rmpA/A2 and PAI detection................................................................ 12 3.3 Correlation between virulence genes on the chromosome .................. 13 3.4 Correlation between virulence genes on the large virulence plasmid ......... 13 3.5 Distribution of host underlying diseases .......................................... 14 3.6 Risk factors for K. pneumoniae pyogenic liver abscess ......................... 15 3.7 Interaction between K. pneumoniae genotype and host underlying disease ..... 16 Chapter 4 Discussion ..............................................................................17 4.1 Roles of Klebsiella pneumoniae genotypes in the pathogenesis of pyogenic liver abscess .................................................................................... 17 4.2 Role of diabetes mellitus ................................................................. 18 4.3 Clinical applications .........................................................................19 4.4 Future directions ............................................................................. 19 References .............................................................................................21 | |
| dc.language.iso | en | |
| dc.title | 克雷伯氏肺炎桿菌基因型在肝膿瘍致病機轉的角色：病例對照研究 | zh_TW |
| dc.title | Role of Klebsiella pneumoniae genotypes in pathogenesis of pyogenic liver abscess: A case-control study | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 鄧麗珍,賴信志,施惟量 | |
| dc.subject.keyword | 克雷伯氏肺炎桿菌,細菌性肝膿瘍,基因型,致病機轉,病例對照研究, | zh_TW |
| dc.subject.keyword | Klebsiella pneumoniae,Pyogenic liver abscess,Genotypes,Pathogenesis,Case-control study, | en |
| dc.relation.page | 49 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2015-01-27 | |
| dc.contributor.author-college | 公共衛生學院 | zh_TW |
| dc.contributor.author-dept | 流行病學與預防醫學研究所 | zh_TW |
| 顯示於系所單位： | 流行病學與預防醫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-103-1.pdf 未授權公開取用 | 5.09 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。