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系統識別號 U0026-0812200915061279
論文名稱(中文) 創傷弧菌之qnr相似基因與細菌對諾酮類抗生素之抗藥性的關聯
論文名稱(英文) Association of a qnr-like gene in Vibrio vulnificus with bacterial resistance to quinolones
校院名稱 成功大學
系所名稱(中) 微生物及免疫學研究所
系所名稱(英) Department of Microbiology & Immunology
學年度 97
學期 1
出版年 98
研究生(中文) 黃千晏
研究生(英文) Chien-Yen Huang
學號 S4695111
學位類別 碩士
語文別 中文
論文頁數 71頁
口試委員 口試委員-鄧景浩
指導教授-何漣漪
口試委員-吳俊忠
口試委員-楊采菱
中文關鍵字 創傷弧菌  諾酮  抗藥性 
英文關鍵字 quinolones  Vibrio vulnificus  qnr-like  resistance  qnr 
學科別分類
中文摘要 諾酮類 (quinolones) 藥物是廣效型抗生素,會藉著結合到DNA gyrase 或topoisomerase IV以抑制DNA進行複製或轉錄等工作。這些藥物被廣泛使用於許多地方,造成抗藥性菌株越來越多。從1998年首度發現靠質體傳送的qnr (quinolone-resistance) 抗藥基因之後,世界各地陸續分離到攜帶此基因的各種菌株。Qnrs是含有五聚重複序列的蛋白,會與DNA gyrase做特異性結合,使得諾酮類藥物無法執行功能。目前已知有三種由質體攜帶的Qnrs:QnrA, QnrB和QnrS,其宿主主要是腸內桿菌科的細菌。之前已發現弧菌屬的某些細菌(包括創傷弧菌CIP103196菌株)的染色體上帶有與qnr相似的基因,推測可能是質體上的qnr基因的來源。創傷弧菌是生活在海水環境中的革蘭氏陰性細菌,也是伺機性病原菌。我們在本實驗室所研究的創傷弧菌YJ016菌株的染色體上也找到了一個qnrA相似基因VVA1469,其胺基酸序列與qnrA1有58%的相同度。觀察此菌株在LB或Muller-Hinton (MH) 培養基中於37℃生長3到12小時過程中此基因的表現量,發現無論在那種培養基中,都是在培養約九小時有最高的表現量。不過VVA1469在MH培養基中的表現量比在LB培養基中低很多。我們以中等複製數的廣泛宿主型質體pIT009及高複製數的pGEM-T easy選殖VVA1469送入大腸桿菌DH5α中,發現宿主對諾酮類藥物的抗性增加約1.5到6倍。另一方面,我們也發現將VVA1469從創傷弧菌的染色體剔除掉之後,突變株對此類藥物的敏感性變得更高。此外,我們也使用蛋白表現誘導系統證明了VVA1469被誘導表現的程度與宿主細菌對此類藥物的抗性呈現正相關性。綜合以上結果顯示,創傷弧菌的qnrA-like基因VVA1469在該菌對諾酮類藥物的抗性上扮演一個角色。
英文摘要 Quinolones are broad-spectrum antibiotics that inhibit DNA replication and transcription by binding to the bacterial DNA gyrase or topoisomerase IV. They are used widely and that lead to the isolation of increasing number of resistant bacterial strains. Since the first report of plasmid-mediated qnr (quinolone-resistance) gene from USA in 1998, strains with this gene have been isolated worldwide. Qnrs are pentapeptide repeats-containing proteins that bind specifically to the DNA gyrase to prevent this enzyme from inhibition by quinolones. Three major groups of Qnrs, QnrA, QnrB and QnrS, have been identified, mainly in Enterobacteriaceae. It has been found that some Vibrionaceae strains, including V. vulnificus strain CIP103196, carried a qnr-like gene in the chromosome, which are possibly the sources of plasmid-mediated qnr genes. Vibrio vulnificus is a gram-negative opportunistic pathogen inhabiting the marine environments. In the genome of V. vulnificus strain YJ016, we have also identified a qnrA-like gene, VVA1469, whose amino acid sequence shares 58% identity with that of QnrA1. The VVA1469 gene was expressed in YJ016 when the bacteria were cultured in LB or Muller-Hinton (MH) broth at 37℃ for 3 h up to 12 h, with the highest expression level at 9 h. However, the expression level of VVA1469 was much lower in bacteria cultured in MH medium than those cultured in LB medium. The MICs of E. coli strain DH5α to quinolones was 1.5- to 6- fold increased when VVA1469 was expressed from pGEM-T easy, a high copy number plasmid, or pIT009, a broad-host-range plasmid of moderate copy number. On the other hand, a VVA1469-knockout V. vulnificus mutant was shown to become highly susceptible to the fluoroquinolones. We also demonstrated with an inducible system that the induction level of VVA1469 was positively correlated with bacterial resistance to quinolones. Collectively, our data suggest that the qnrA-like gene in V. vulnificus might play a role in the resistance of this organism to quinolones.
論文目次 中文摘要 i
英文摘要 ii
誌謝 iV
目錄 v
表目錄 ix
圖目錄 x
符號及縮寫 xi
緒論 1
材料與方法 10
(1)實驗菌株與質體 10
(2)實驗菌種的培養與保存方法 10
(3)實驗方法 10
◆ 基礎核酸技術 10
1.小量純化質體DNA(TENS法)10
2.以商業化套組萃取質體DNA 11
3.大量純化質體DNA 11
4.創傷弧菌染色體DNA之萃取 12
5.以商業套件純化染色體DNA 13
6.聚合連鎖反應(PCR) 13
7.PCR放大片段之選殖(TA cloning) 14
8.限制切割DNA 14
9.DNA電泳分析 15
10.DNA片段之回收 15
11.DNA片段之去磷酸化反應 16
12.DNA接合反應 16
13.任意致突變法(Random mutagenesis) 16
14.細菌RNA之萃取 17
15.細菌RNA反轉錄作用及聚合連鎖反應(RT-PCR) 18
◆ 雜交試驗 18
1.DNA探針製備 18
2.南方雜交法 19
◆ 質體轉移方法 19
1.熱休克轉形作用(heat shock)19
2.電擊轉形作用(electroporation) 20
3.接合生殖作用(conjugation) 21
(4)創傷弧菌突變株之製備 21
(5)互補作用 22
(6)細菌生長曲線之測定 22
(7)抗生素抗藥性之測試 22
1.接種源的製備 23
2.以瓊脂稀釋法(agar dilution method)測定最低抑菌濃度
(MIC) 23
(8)誘導式表現質體之構築 23
1.誘導式表現質體pCY04之構築 23
2.誘導式表現質體pCY09之構築 24
(9)資料分析 24
1.DNA序列決定 24
2.DNA promoter之預測 25
3.胺基酸序列之分析 25
4.胺基酸序列比對及演化樹 25
結果 26
I. 創傷弧菌YJ016菌株之VVA1469基因的生物資訊學分析 26
1.胺基酸序列之分析 26
2.與QnrA1, QnrB1, QnrS1, QnrVV胺基酸序列之相似度 26
II.創傷弧菌的VVA1469基因之表現 26
III.YJ016對quinolone類抗生素的抗性 27
IV.VVA1469基因對E. coli DH5α對quinolone類抗生素之感受性的
影響 27
1.VVA1469基因在E. coli DH5α中的表現量 27
2.DH5α(pCY01)和DH5α(pCY02)對quinolone類抗生素的敏感性 27
V.創傷弧菌YJ016ΔVVA1469突變株之分離及其抗藥性之分析 28
1.創傷弧菌YJ016ΔVVA1469突變株的分離 28
2.創傷弧菌YJ016ΔVVA1469突變株之VVA1469補償株
(complementary strain)的分離 28
3.VVA1469基因與創傷弧菌YJ016對quinolone類抗生素之敏感性
的關聯 29
4.創傷弧菌VVA1469突變株的生長情形 29
VI.Mueller-Hinton(MH)agar對於VVA1469表現之影響 30
1.MH agar對於VVA1469表現之影響 30
2.創傷弧菌野生株在MH broth中之生長情形 30
VII. VVA1469基因之表現量與創傷弧菌對quinolone類抗生素之敏
感性的相關性 30
1.誘導性表現VVA1469之質體pCY09的構築 31
2.誘發VVA1469之表現與quinolone類抗生素對該菌株之MIC之測
試 31
VIII.抗性增加突變菌株篩選之結果 31
討論 33
參考文獻 39
表 46
圖 54
附錄 68
自述 71
參考文獻 1. Amaro, C., and E. G. Biosca. 1996. Vibrio vulnificus biotype 2, pathogenic for eels, is also an opportunistic pathogen for humans. Appl Environ Microbiol 62:1454-1457.
2. Amaro, C., E. G. Biosca, B. Fouz, and E. Garay. 1992. Electrophoretic analysis of heterogeneous lipopolysaccharides from various strains of Vibrio vulnificus biotypes 1 and 2 by silver staining and immunoblotting. Curr Microbiol 25:99-104.
3. Amaro, C., L. I. Hor, E. Marco-Noales, T. Bosque, B. Fouz, and E. Alcaide. 1999. Isolation of Vibrio vulnificus serovar E from aquatic habitats in Taiwan. Appl Environ Microbiol 65:1352-1355.
4. Arsene, S., and R. Leclercq. 2007. Role of a qnr-like gene in the intrinsic resistance of Enterococcus faecalis to fluoroquinolones. Antimicrob Agents Chemother 51:3254-3258.
5. Bateman, A., A. G. Murzin, and S. A. Teichmann. 1998. Structure and distribution of pentapeptide repeats in bacteria. Protein Sci 7:1477-1480.
6. Bisharat, N., V. Agmon, R. Finkelstein, R. Raz, G. Ben-Dror, L. Lerner, S. Soboh, R. Colodner, D. N. Cameron, D. L. Wykstra, D. L. Swerdlow, and J. J. Farmer, 3rd. 1999. Clinical, epidemiological, and microbiological features of Vibrio vulnificus biogroup 3 causing outbreaks of wound infection and bacteraemia in Israel. Israel Vibrio Study Group. Lancet 354:1421-1424.
7. Blake, P. A., M. H. Merson, R. E. Weaver, D. G. Hollis, and P. C. Heublein. 1979. Disease caused by a marine Vibrio. Clinical characteristics and epidemiology. N Engl J Med 300:1-5.
8. Bullen, J. J., P. B. Spalding, C. G. Ward, and J. M. Gutteridge. 1991. Hemochromatosis, iron and septicemia caused by Vibrio vulnificus. Arch Intern Med 151:1606-1609.
9. Cattoir, V., L. Poirel, C. Aubert, C. J. Soussy, and P. Nordmann. 2008. Unexpected occurrence of plasmid-mediated quinolone resistance determinants in environmental Aeromonas spp. Emerg Infect Dis 14:231-237.
10. Cattoir, V., L. Poirel, D. Mazel, C. J. Soussy, and P. Nordmann. 2007. Vibrio splendidus as the source of plasmid-mediated QnrS-like quinolone resistance determinants. Antimicrob Agents Chemother 51:2650-2651.
11. Cattoir, V., L. Poirel, and P. Nordmann. 2007. In-vitro mutagenesis of qnrA and qnrS genes and quinolone resistance in Escherichia coli. Clin Microbiol Infect 13:940-943.
12. Cavaco, L. M., H. Hasman, S. Xia, and F. M. Aarestrup. 2008. QnrD, a novel gene conferring transferable quinolone resistance in Salmonella enterica serovars Kentucky and Bovismorbificans of human origin. Antimicrob Agents Chemother.
13. Chan, T. Y., D. P. Chow, K. C. Ng, K. W. Pang, and G. A. McBride. 1994. Vibrio vulnificus septicemia in a patient with liver cirrhosis. Southeast Asian J Trop Med Public Health 25:215-216.
14. Chen, C. Y., K. M. Wu, Y. C. Chang, C. H. Chang, H. C. Tsai, T. L. Liao, Y. M. Liu, H. J. Chen, A. B. Shen, J. C. Li, T. L. Su, C. P. Shao, C. T. Lee, L. I. Hor, and S. F. Tsai. 2003. Comparative genome analysis of Vibrio vulnificus, a marine pathogen. Genome Res 13:2577-2587.
15. Chuang, Y. C., C. Y. Yuan, C. Y. Liu, C. K. Lan, and A. H. Huang. 1992. Vibrio vulnificus infection in Taiwan: report of 28 cases and review of clinical manifestations and treatment. Clin Infect Dis 15:271-276.
16. Degnen, G. E., and E. C. Cox. 1974. Conditional mutator gene in Escherichia coli: isolation, mapping, and effector studies. J Bacteriol 117:477-487.
17. Donnenberg, M. S., and J. B. Kaper. 1991. Construction of an eae deletion mutant of enteropathogenic Escherichia coli by using a positive-selection suicide vector. Infect Immun 59:4310-4317.
18. Drlica, K., and X. Zhao. 1997. DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev 61:377-392.
19. Elmore, S. P., J. A. Watts, L. M. Simpson, and J. D. Oliver. 1992. Reversal of hypotension induced by Vibrio vulnificus lipopolysaccharide in the rat by inhibition of nitric oxide synthase. Microb Pathog 13:391-397.
20. Gander, R. M., and M. T. LaRocco. 1989. Detection of piluslike structures on clinical and environmental isolates of Vibrio vulnificus. J Clin Microbiol 27:1015-1021.
21. Garrido, M. C., M. Herrero, R. Kolter, and F. Moreno. 1988. The export of the DNA replication inhibitor Microcin B17 provides immunity for the host cell. EMBO J 7:1853-1862.
22. Guzman, L. M., D. Belin, M. J. Carson, and J. Beckwith. 1995. Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter. J Bacteriol 177:4121-4130.
23. Halow, K. D., R. C. Harner, and L. J. Fontenelle. 1996. Primary skin infections secondary to Vibrio vulnificus: the role of operative intervention. J Am Coll Surg 183:329-334.
24. Hanahan, D. 1983. Studies on transformation of Escherichia coli with plasmids. J Mol Biol 166:557-580.
25. Hata, M., M. Suzuki, M. Matsumoto, M. Takahashi, K. Sato, S. Ibe, and K. Sakae. 2005. Cloning of a novel gene for quinolone resistance from a transferable plasmid in Shigella flexneri 2b. Antimicrob Agents Chemother 49:801-803.
26. Hegde, S. S., M. W. Vetting, S. L. Roderick, L. A. Mitchenall, A. Maxwell, H. E. Takiff, and J. S. Blanchard. 2005. A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. Science 308:1480-1483.
27. Hlady, W. G., and K. C. Klontz. 1996. The epidemiology of Vibrio infections in Florida, 1981-1993. J Infect Dis 173:1176-1183.
28. Hollis, D. G., R. E. Weaver, C. N. Baker, and C. Thornsberry. 1976. Halophilic Vibrio species isolated from blood cultures. J Clin Microbiol 3:425-431.
29. Hooper, D. C. 2001. Emerging mechanisms of fluoroquinolone resistance. Emerg Infect Dis 7:337-341.
30. Hor, L. I., Y. K. Chang, C. C. Chang, H. Y. Lei, and J. T. Ou. 2000. Mechanism of high susceptibility of iron-overloaded mouse to Vibrio vulnificus infection. Microbiol Immunol 44:871-878.
31. Hsueh, P. R., C. Y. Lin, H. J. Tang, H. C. Lee, J. W. Liu, Y. C. Liu, and Y. C. Chuang. 2004. Vibrio vulnificus in Taiwan. Emerg Infect Dis 10:1363-1368.
32. Hu, L. F., J. B. Li, Y. Ye, and X. Li. 2007. Mutations in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV in clinical strains of fluoroquinolone-resistant Shigella in Anhui, China. J Microbiol 45:168-170.
33. Jacoby, G. A., K. E. Walsh, D. M. Mills, V. J. Walker, H. Oh, A. Robicsek, and D. C. Hooper. 2006. qnrB, another plasmid-mediated gene for quinolone resistance. Antimicrob Agents Chemother 50:1178-1182.
34. Jiang, Y., Z. Zhou, Y. Qian, Z. Wei, Y. Yu, S. Hu, and L. Li. 2008. Plasmid-mediated quinolone resistance determinants qnr and aac(6')-Ib-cr in extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in China. J Antimicrob Chemother 61:1003-1006.
35. Kaspar, C. W., and M. L. Tamplin. 1993. Effects of temperature and salinity on the survival of Vibrio vulnificus in seawater and shellfish. Appl Environ Microbiol 59:2425-2429.
36. Kim, Y. R., S. E. Lee, H. Kook, J. A. Yeom, H. S. Na, S. Y. Kim, S. S. Chung, H. E. Choy, and J. H. Rhee. 2008. Vibrio vulnificus RTX toxin kills host cells only after contact of the bacteria with host cells. Cell Microbiol 10:848-862.
37. Klontz, K. C., S. Lieb, M. Schreiber, H. T. Janowski, L. M. Baldy, and R. A. Gunn. 1988. Syndromes of Vibrio vulnificus infections. Clinical and epidemiologic features in Florida cases, 1981-1987. Ann Intern Med 109:318-323.
38. Koenig, K. L., J. Mueller, and T. Rose. 1991. Vibrio vulnificus sepsis presenting as leg pain and lower extremity rash. Am J Emerg Med 9:523-524.
39. Kumamoto, K. S., and D. J. Vukich. 1998. Clinical infections of Vibrio vulnificus: a case report and review of the literature. J Emerg Med 16:61-66.
40. Lee, J. H., J. B. Rho, K. J. Park, C. B. Kim, Y. S. Han, S. H. Choi, K. H. Lee, and S. J. Park. 2004. Role of flagellum and motility in pathogenesis of Vibrio vulnificus. Infect Immun 72:4905-4910.
41. Lin, W., K. J. Fullner, R. Clayton, J. A. Sexton, M. B. Rogers, K. E. Calia, S. B. Calderwood, C. Fraser, and J. J. Mekalanos. 1999. Identification of a vibrio cholerae RTX toxin gene cluster that is tightly linked to the cholera toxin prophage. Proc Natl Acad Sci U S A 96:1071-1076.
42. Linkous, D. A., and J. D. Oliver. 1999. Pathogenesis of Vibrio vulnificus. FEMS Microbiol Lett 174:207-214.
43. Manoil, C., and J. Beckwith. 1985. TnphoA: a transposon probe for protein export signals. Proc Natl Acad Sci U S A 82:8129-8133.
44. Martinez-Martinez, L., A. Pascual, and G. A. Jacoby. 1998. Quinolone resistance from a transferable plasmid. Lancet 351:797-799.
45. McDonald, L. C., M. T. Chen, T. L. Lauderdale, and M. Ho. 2001. The use of antibiotics critical to human medicine in food-producing animals in Taiwan. J Microbiol Immunol Infect 34:97-102.
46. Musher, D. M. 1989. Cutaneous manifestations of bacterial sepsis. Hosp Pract (Off Ed) 24:71-75, 80-72, 92 passim.
47. Nikaido, H. 2003. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 67:593-656.
48. Nordmann, P., and L. Poirel. 2005. Emergence of plasmid-mediated resistance to quinolones in Enterobacteriaceae. J Antimicrob Chemother 56:463-469.
49. O'Neill, K. R., S. H. Jones, and D. J. Grimes. 1992. Seasonal incidence of Vibrio vulnificus in the Great Bay estuary of New Hampshire and Maine. Appl Environ Microbiol 58:3257-3262.
50. Perichon, B., P. Courvalin, and M. Galimand. 2007. Transferable resistance to aminoglycosides by methylation of G1405 in 16S rRNA and to hydrophilic fluoroquinolones by QepA-mediated efflux in Escherichia coli. Antimicrob Agents Chemother 51:2464-2469.
51. Poirel, L., A. Liard, J. M. Rodriguez-Martinez, and P. Nordmann. 2005. Vibrionaceae as a possible source of Qnr-like quinolone resistance determinants. J Antimicrob Chemother 56:1118-1121.
52. Poirel, L., J. M. Rodriguez-Martinez, H. Mammeri, A. Liard, and P. Nordmann. 2005. Origin of plasmid-mediated quinolone resistance determinant QnrA. Antimicrob Agents Chemother 49:3523-3525.
53. Poole, K. 2000. Efflux-mediated resistance to fluoroquinolones in gram-negative bacteria. Antimicrob Agents Chemother 44:2233-2241.
54. Robicsek, A., G. A. Jacoby, and D. C. Hooper. 2006. The worldwide emergence of plasmid-mediated quinolone resistance. Lancet Infect Dis 6:629-640.
55. Robicsek, A., J. Strahilevitz, G. A. Jacoby, M. Macielag, D. Abbanat, C. H. Park, K. Bush, and D. C. Hooper. 2006. Fluoroquinolone-modifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase. Nat Med 12:83-88.
56. Rodkhum, C., T. Maki, I. Hirono, and T. Aoki. 2008. gyrA and parC associated with quinolone resistance in Vibrio anguillarum. J Fish Dis 31:395-399.
57. Rodriguez-Martinez, J. M., C. Pichardo, I. Garcia, M. E. Pachon-Ibanez, F. Docobo-Perez, A. Pascual, J. Pachon, and L. Martinez-Martinez. 2008. Activity of ciprofloxacin and levofloxacin in experimental pneumonia caused by Klebsiella pneumoniae deficient in porins, expressing active efflux and producing QnrA1. Clin Microbiol Infect 14:691-697.
58. Rodriguez-Martinez, J. M., C. Velasco, A. Briales, I. Garcia, M. C. Conejo, and A. Pascual. 2008. Qnr-like pentapeptide repeat proteins in gram-positive bacteria. J Antimicrob Chemother 61:1240-1243.
59. Saga, T., M. Kaku, Y. Onodera, S. Yamachika, K. Sato, and H. Takase. 2005. Vibrio parahaemolyticus chromosomal qnr homologue VPA0095: demonstration by transformation with a mutated gene of its potential to reduce quinolone susceptibility in Escherichia coli. Antimicrob Agents Chemother 49:2144-2145.
60. Shao, C. P., and L. I. Hor. 2000. Metalloprotease is not essential for Vibrio vulnificus virulence in mice. Infect Immun 68:3569-3573.
61. Shao, C. P., and L. I. Hor. 2001. Regulation of metalloprotease gene expression in Vibrio vulnificus by a Vibrio harveyi LuxR homologue. J Bacteriol 183:1369-1375.
62.Simon, L. M., J. Nemcsok, and L. Boross. 1983. Studies on the effect of paraquat on glycogen mobilization in liver of common carp (Cyprinus carpio L.). Comp Biochem Physiol C 75:167-169.
63. Simpson, L. M., and J. D. Oliver. 1983. Siderophore production by Vibrio vulnificus. Infect Immun 41:644-649.
64. Sorlozano, A., J. Gutierrez, A. Jimenez, J. de Dios Luna, and J. L. Martinez. 2007. Contribution of a new mutation in parE to quinolone resistance in extended-spectrum-beta-lactamase-producing Escherichia coli isolates. J Clin Microbiol 45:2740-2742.
65. Strom, M. S., and R. N. Paranjpye. 2000. Epidemiology and pathogenesis of Vibrio vulnificus. Microbes Infect 2:177-188.
66. Sulavik, M. C., C. Houseweart, C. Cramer, N. Jiwani, N. Murgolo, J. Greene, B. DiDomenico, K. J. Shaw, G. H. Miller, R. Hare, and G. Shimer. 2001. Antibiotic susceptibility profiles of Escherichia coli strains lacking multidrug efflux pump genes. Antimicrob Agents Chemother 45:1126-1136.
67. Tang, H. J., M. C. Chang, W. C. Ko, K. Y. Huang, C. L. Lee, and Y. C. Chuang. 2002. In vitro and in vivo activities of newer fluoroquinolones against Vibrio vulnificus. Antimicrob Agents Chemother 46:3580-3584.
68. Tran, J. H., and G. A. Jacoby. 2002. Mechanism of plasmid-mediated quinolone resistance. Proc Natl Acad Sci U S A 99:5638-5642.
69. Tran, J. H., G. A. Jacoby, and D. C. Hooper. 2005. Interaction of the plasmid-encoded quinolone resistance protein Qnr with Escherichia coli DNA gyrase. Antimicrob Agents Chemother 49:118-125.
70. Tran, J. H., G. A. Jacoby, and D. C. Hooper. 2005. Interaction of the plasmid-encoded quinolone resistance protein QnrA with Escherichia coli topoisomerase IV. Antimicrob Agents Chemother 49:3050-3052.
71. Turiel, E., A. Martin-Esteban, G. Bordin, and A. R. Rodriguez. 2004. Stability of fluoroquinolone antibiotics in river water samples and in octadecyl silica solid-phase extraction cartridges. Anal Bioanal Chem 380:123-128.
72. Vollberg, C. M., and J. L. Herrera. 1997. Vibrio vulnificus infection: an important cause of septicemia in patients with cirrhosis. South Med J 90:1040-1042.
73. Warnock, E. W., 3rd, and T. L. MacMath. 1993. Primary Vibrio vulnificus septicemia. J Emerg Med 11:153-156.
74. Willmott, C. J., and A. Maxwell. 1993. A single point mutation in the DNA gyrase A protein greatly reduces binding of fluoroquinolones to the gyrase-DNA complex. Antimicrob Agents Chemother 37:126-127.
75. Wright, A. C., L. M. Simpson, and J. D. Oliver. 1981. Role of iron in the pathogenesis of Vibrio vulnificus infections. Infect Immun 34:503-507.
76. Wu, J. J., W. C. Ko, C. S. Chiou, H. M. Chen, L. R. Wang, and J. J. Yan. 2008. Emergence of Qnr determinants in human Salmonella isolates in Taiwan. J Antimicrob Chemother 62:1269-1272.
77. Wu, J. J., W. C. Ko, S. H. Tsai, and J. J. Yan. 2007. Prevalence of plasmid-mediated quinolone resistance determinants QnrA, QnrB, and QnrS among clinical isolates of Enterobacter cloacae in a Taiwanese hospital. Antimicrob Agents Chemother 51:1223-1227.
78. Wu, J. J., W. C. Ko, H. M. Wu, and J. J. Yan. 2008. Prevalence of Qnr determinants among bloodstream isolates of Escherichia coli and Klebsiella pneumoniae in a Taiwanese hospital, 1999-2005. J Antimicrob Chemother 61:1234-1239.
79. Xu, X., S. Wu, X. Ye, Y. Liu, W. Shi, Y. Zhang, and M. Wang. 2007. Prevalence and expression of the plasmid-mediated quinolone resistance determinant qnrA1. Antimicrob Agents Chemother 51:4105-4110.
80. Yamane, K., J. Wachino, S. Suzuki, K. Kimura, N. Shibata, H. Kato, K. Shibayama, T. Konda, and Y. Arakawa. 2007. New plasmid-mediated fluoroquinolone efflux pump, QepA, found in an Escherichia coli clinical isolate. Antimicrob Agents Chemother 51:3354-3360.
81. Yoshida, H., M. Bogaki, M. Nakamura, L. M. Yamanaka, and S. Nakamura. 1991. Quinolone resistance-determining region in the DNA gyrase gyrB gene of Escherichia coli. Antimicrob Agents Chemother 35:1647-1650.
82. Young, H. K. 1993. Antimicrobial resistance spread in aquatic environments. J Antimicrob Chemother 31:627-635.
83. 王信斌, 賴宣陽, 陳信志, 周秀冠. 2008. 禽畜水產食品中動物用藥Quinolone類之殘留量調查. 藥物食品檢驗局調查研究年報26:295-305.
84. 陳銘祥. 2006. 創傷弧菌中誘導式表現系統之建立. 成功大學微生物暨免疫學研究所碩士論文.
85. Clinical and Laboratory Standards Institute. Performances standards for antimicrobial susceptibility testing; seventeenrth informational supplement M100–S17. Wayne (PA): The Institute; 2007.
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