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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 鄧麗珍(Lee-Jene Teng) | |
| dc.contributor.author | Kin-Hong Leong | en |
| dc.contributor.author | 梁健雄 | zh_TW |
| dc.date.accessioned | 2021-06-15T16:39:48Z | - |
| dc.date.available | 2018-09-25 | |
| dc.date.copyright | 2015-09-25 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-11 | |
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Hughes, Genetic and phenotypic identification of fusidic acid-resistant mutants with the small-colony-variant phenotype in Staphylococcus aureus. Antimicrob Agents Chemother, 2007. 51(12): p. 4438-46. 19. O'Neill, A.J., et al., Genetic basis of resistance to fusidic acid in staphylococci. Antimicrob Agents Chemother, 2007. 51(5): p. 1737-40. 20. Castanheira, M., et al., Occurrence and molecular characterization of fusidic acid resistance mechanisms among Staphylococcus spp. from European countries (2008). J Antimicrob Chemother, 2010. 65(7): p. 1353-8. 21. Castanheira, M., et al., Fusidic acid resistance rates and prevalence of resistance mechanisms among Staphylococcus spp. isolated in North America and Australia, 2007-2008. Antimicrob Agents Chemother, 2010. 54(9): p. 3614-7. 22. Chen, H.J., et al., Identification of fusB-mediated fusidic acid resistance islands in Staphylococcus epidermidis isolates. Antimicrob Agents Chemother, 2011. 55(12): p. 5842-9. 23. Chen, H.J., et al., New structure of phage-related islands carrying fusB and a virulence gene in fusidic acid-resistant Staphylococcus epidermidis. Antimicrob Agents Chemother, 2013. 57(11): p. 5737-9. 24. Yazdankhah, S.P., et al., Fusidic acid resistance, mediated by fusB, in bovine coagulase-negative staphylococci. J Antimicrob Chemother, 2006. 58(6): p. 1254-6. 25. O'Brien, F.G., et al., Genetic characterization of the fusidic acid and cadmium resistance determinants of Staphylococcus aureus plasmid pUB101. J Antimicrob Chemother, 2002. 50(3): p. 313-21. 26. Coutant, C., et al., Disk diffusion interpretive criteria for fusidic acid susceptibility testing of staphylococci by the National Committee for Clinical Laboratory Standards method. Diagn Microbiol Infect Dis, 1996. 25(1): p. 9-13. 27. Cavanagh, J.P., et al., Core genome conservation of Staphylococcus haemolyticus limits sequence based population structure analysis. J Microbiol Methods, 2012. 89(3): p. 159-66. 28. Novick, R.P., G.E. Christie, and J.R. Penadés, The phage-related chromosomal islands of Gram-positive bacteria. Nat Rev Micro, 2010. 8(8): p. 541-551. 29. de Almeida, L.M., et al., Complete Genome Sequence of Linezolid-Susceptible Staphylococcus haemolyticus Sh29/312/L2, a Clonal Derivative of a Linezolid-Resistant Clinical Strain. Genome Announc, 2015. 3(3). 30. Takeuchi, F., et al., Whole-genome sequencing of staphylococcus haemolyticus uncovers the extreme plasticity of its genome and the evolution of human-colonizing staphylococcal species. J Bacteriol, 2005. 187(21): p. 7292-308. 31. Hauschild, T. and S. Stepanovic, Identification of Staphylococcus spp. by PCR-restriction fragment length polymorphism analysis of dnaJ gene. J Clin Microbiol, 2008. 46(12): p. 3875-9. 32. Shah, M.M., et al., dnaJ gene sequence-based assay for species identification and phylogenetic grouping in the genus Staphylococcus. Int J Syst Evol Microbiol, 2007. 57(Pt 1): p. 25-30. 33. Shin, J.H., et al., Identification of coagulase-negative staphylococci isolated from continuous ambulatory peritoneal dialysis fluid using 16S ribosomal RNA, tuf, and SodA gene sequencing. Perit Dial Int, 2011. 31(3): p. 340-6. 34. Dupont, C., et al., Identification of clinical coagulase-negative staphylococci, isolated in microbiology laboratories, by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and two automated systems. Clin Microbiol Infect, 2010. 16(7): p. 998-1004. 35. Argemi, X., et al., Implementation of MALDI-TOF MS in routine clinical laboratories improves identification of coagulase negative staphylococci and reveals the pathogenic role of Staphylococcus lugdunensis. J Clin Microbiol, 2015. 36. The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 5.0. 2015: p. 17-21. 37. O'Neill, A.J. and I. Chopra, Molecular basis of fusB-mediated resistance to fusidic acid in Staphylococcus aureus. Molecular Microbiology, 2006. 59(2): p. 664-676. 38. Pace, N., et al., The analysis of natural microbial populations by rRNA sequences. Advances in microbial ecology, 1986. 9: p. 1-55. 39. Brakstad, O.G., K. Aasbakk, and J.A. Maeland, Detection of Staphylococcus aureus by polymerase chain reaction amplification of the nuc gene. J Clin Microbiol, 1992. 30(7): p. 1654-60. 40. Liu, D., et al., Use of a putative transcriptional regulator gene as target for specific identification of Staphylococcus epidermidis. Lett Appl Microbiol, 2006. 43(3): p. 325-30. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/53023 | - |
| dc.description.abstract | 臨床上分離之凝固酶陰性葡萄球菌(coagulase-negative staphylococci, CoNS)常被認為是污染而非有意義的病原菌，但近年來發現其在臨床上的重要性，如表皮葡萄球菌(Staphylococcus epidermidis)可以造成菌血症、感染性心內膜炎等；里昴葡萄球菌(Staphylococcus lugdunensis)可以造成感染性心內膜炎、腦膜炎及皮膚與軟組織感染等。因此，準確的鑑定出凝固酶陰性葡萄球菌對疾病診斷及流行病學等均具有重要意義。
夫西地酸(fusidic acid)藉由與EF-G-GTP/GDP-核醣體結合，使EF-G/GDP無法離開核醣體，從而抑制細菌的蛋白蛋合成，臨床上主要用於治療葡萄球菌所引起的皮膚感染或較為嚴重的全身性症狀。細菌可經由表現保護藥物作用標的之蛋白質(FusB-protein family)來對抗夫西地酸的作用，因而限制了夫西地酸在臨床上的使用，瞭解抗藥基因在葡萄球菌的盛行率、抗藥程度與分析抗藥基因結構等具有很重要的意義。 本研究收集了臺大醫院2010年至2012年的凝固酶陰性葡萄球菌，利用分子鑑定方法對收集到的菌株重新鑑定後，共497株，其中242株對夫西地酸為抗性。討論其夫西地酸抗藥基因(fusB、fusC、fusD與fusF)的盛行率及抗藥程度的關聯性，發現在菌種間具有特定的趨勢。在頭部葡萄球菌解脲亞種(Staphylococcus capitis subsp. urealyticus，49/51，96.1%)、表皮葡萄球菌(Staphylococcus epidermidis，89/89，100%)與溶血葡萄球菌(Staphylococcus haemolyticus，65/70，92.9%)裡，主要帶有fusB引起抗藥(MIC範圍為2至32μg/ml)。在10株人葡萄球菌人亞種(Staphylococcus hominis subsp. hominis)中，有9株(90%)因為帶有fusC造成抗藥(MIC範圍為2至16μg/ml)。於8株腐生葡萄球菌(Staphylococcus saprophyticus)中，全都因為帶有fusD導致抗藥(MIC範圍為2至4μg/ml)。而在11株科氏葡萄球菌解脲亞種(Staphylococcus cohnii subsp. urealyticus)中，有10株因為帶有fusF產生抗藥(MIC範圍為2至4μg/ml)。FusB-family protein導致的夫西地酸抗藥程度屬於低抗藥性。根據aj1-LP-fusB片段分為三個型別，在表皮葡萄球菌裡發現，相較於帶有第一型及第三型aj1-LP-fusB片段之菌株(MICs為2至8μg/ml)，帶有第二型之菌株可表現相對較高程度抗藥(MICs為4至16μg/ml)。 對於溶血葡萄球菌帶有fusB基因結構的研究比較少，故以PFGE進行菌株分型，發現65株共可分為6種pulsotypes，以pulsotype E (51/65)所含菌株數最多，再利用LA-PCR與Inverse-PCR分析了一株臨床菌株之fusB基因結構，發現其位在smpB下游，與一自巴西分離出之溶血葡萄球菌Sh29/312/L2結構十分相似。 在208株帶有fusB抗藥基因的菌株中，83株(39.9%)嵌入groEL基因下游之抗藥島嶼(resistance islands)，1株(0.48%)嵌入rpsR基因下游之抗藥島嶼，49株(23.6%)嵌入smpB基因下游之抗藥島嶼，沒有發現嵌在pNVH96質體上，還有75株(36.1%)的fusB抗藥基因嵌在未知的位置。 | zh_TW |
| dc.description.abstract | Coagulase-negative staphylococci (CoNS) isolates from clinical specimens are usually considered as contaminants. However, CoNS have, in recent years, been recognized as emerging opportunistic pathogens in nosocomial infections. Staphylococcus epidermidis is well known as a cause of bacteremia and infective endocarditis (IE), and other CoNS such as Staphylococcus lugdunensis, S. hominis, and S. haemolyticus are also associated with various infections. Thus, accurate identification of CoNS to the species level is essential in investigating clinical signigicance, progress of disease, and epidemiologic characteristics.
Fusidic acid is a steroid antibiotic used as topical agent for skin infection and systemic treatment against staphylococcal infection. Fusidic acid inhibits bacterial protein synthesis by preventing release of EF-G/GDP complex from ribosome. Resistance to fusidic acid results from alternation of drug target site or protection of drug target site by FusB-family protein. The emergence of fusidic acid resistance restricts the clinical usage. It is important to clarify the prevalence of the resistance determinants, the resistance level, and genetic organizations of resistance determinants. In this study, clinical isolates of CoNS were recovered from NTUH in 2010 to 2012. A total of 497 CoNS were collected. Among 497 CoNS, 242 were resistant to fusidic acid. Resistance determinants of fusB, fusC, fusD and fusF were determined by PCR. Most Staphylcoccus capitis subsp. urealyticus (49/51, 96.1%), S. epidermidis (89/89, 100%) and S. haemolyticus (65/70. 92.9%) carried fusB (MIC ranges from 2 to 32μg/ml). Among 10 Staphylococcus hominis subsp. hominis, 9 (90%) isolates carried fusC (MIC ranges from 2 to 16μg/ml). All isolates of S. saprophyticus (8) carried fusD (MIC ranges from 2 to 4μg/ml) and 10 isolates of Staphylococcus cohnii subsp. urealyticus carried fusF (MIC ranges from 2 to 4μg/ml). Low-level resistance to fusidic acid (MICs≦32μg/ml) was found in FusB-family protein positive isolate. According to sequence of aj1-LP-fusB region, fusB carrying isolates can be divided in three types. Staphylococcus epidermidis isolates with type II aj1 displayed slightly higher-level of resistance to fusidic acid (MIC ranges from 4 to 16μg/ml) compared with those with type I or type III aj1 (MIC ranges from 2 to 8μg/ml). Only a few reports of S. haemolyticus’fusB were announced. Here we analyze the genetic relatedness using PFGE, 65 isolates can be separated into 6 groups. The pulsotype E was the most predominant (51/65). Using LA-PCR and Inverse-PCR to analyse the fusB structure of a clinical isolate. The results indicated that the fusB was located downstream of smpB, and displaying high similarity with that in S. haemolyticus Sh29/312/L2 isolated from Brazil. Among 208 isolates, 83 (39.9%) fusB resistance islands (RIs) were located downstream of groEL, 1 (0.48%) was located downstream of rpsR, and 49 (23.6%) were located downstream of smpB. 75 (36.1%) remained unidentified. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T16:39:48Z (GMT). No. of bitstreams: 1 ntu-104-R02424004-1.pdf: 2723005 bytes, checksum: f86675f9a1fbca27f77ffa2e546c20fa (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 致謝 I
英文摘要 II 中文摘要 V 目錄 VII 表目錄 IX 圖目錄 X 第一章、緒論 1 第二章、研究動機與實驗設計 5 第三章、實驗材料與方法 6 第四章、實驗結果 45 4.1 凝固酶陰性葡萄球菌菌種鑑定 45 4.1.1 分子鑑定結果與臨床鑑定結果比較 45 4.2凝固酶陰性葡萄球菌所帶的夫西地酸抗藥基因 45 4.2.1凝固酶陰性葡萄球菌之抗藥程度(MIC)分析 45 4.2.2夫西地酸抗藥基因的分佈情況 46 4.2.3夫西地酸抗藥基因與MIC的關聯 46 4.2.4 aj1-LP-fusB片段分析 47 4.4 溶血葡萄球菌分型 47 4.4.1 SmaI-PFGE分型結果 48 4.4.2 MLST分型結果 48 4.5 溶血葡萄球菌臨床菌株MY4018066所帶的fusB基因結構分析 48 4.5.1 S1 nuclease-PFGE分析 48 4.5.2 MY4018066之fusB基因結構分析 49 4.5.3 MY4018066之fusB基因結構與已發佈的比較 49 4.5.4 南方墨點法-溶血葡萄球菌質體 50 4.6 fusB在凝固酶陰性葡萄球菌的基因分析 50 4.6.1 fusB嵌入的基因結構 50 4.6.2 fusB嵌入的基因結構與aj1-LP-fusB型別在各菌種的關聯 51 第五章、討論 52 第六章、實驗圖表 56 第七章、參考文獻 82 | |
| dc.language.iso | zh-TW | |
| dc.subject | 凝固?陰性葡萄球菌 | zh_TW |
| dc.subject | 鑑定 | zh_TW |
| dc.subject | 夫西地酸 | zh_TW |
| dc.subject | fusB | zh_TW |
| dc.subject | smpB | zh_TW |
| dc.subject | 溶血葡萄球菌 | zh_TW |
| dc.subject | Staphylococcus haemolyticus | en |
| dc.subject | Coagulase-negative staphylococci (CoNS) | en |
| dc.subject | identification | en |
| dc.subject | fusidic acid | en |
| dc.subject | fusB | en |
| dc.subject | smpB | en |
| dc.title | 凝固酶陰性葡萄球菌之夫西地酸抗藥基因分析 | zh_TW |
| dc.title | Fusidic acid resistance determinants in clinical isolates of coagulase-negative staphylococci | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 廖淑貞(Shwu-Jen Liaw),邱浩傑(Hao-Chieh Chiu),曾嵩斌(Sung-Pin Tseng) | |
| dc.subject.keyword | 凝固?陰性葡萄球菌,鑑定,夫西地酸,fusB,smpB,溶血葡萄球菌, | zh_TW |
| dc.subject.keyword | Coagulase-negative staphylococci (CoNS),identification,fusidic acid,fusB,smpB,Staphylococcus haemolyticus, | en |
| dc.relation.page | 85 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-08-11 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
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