새로운 플루오로 퀴놀론계 항균제에 대한 내성 MRSA 균주의 In Vitro 선발과 그 내성 기전 분석 = In Vitro Selection of MRSA Strains Resistant to Some New Fluoroquinolone Antibiotics and Characterization of their Resistance Mechanisms

다국어 초록 (Multilingual Abstract)

Clinically isolated methicillin-resistant Staphylococcus aureus strains were exposed to subinhibitory concentration of DW286, DW-224a, gemifloxacin, trovafloxacin, sparfloxacin and ciprofloxacin during 26- to 39-days period. Subculturing led to resistance development, and most of the selected mutants were above susceptible breakpoints. Selected mutants had broad cross resistance to other quinolone antibiotics and only one mutant was completely susceptible to all fluoroquinolones. Twenty five among 42 mutants revealed mutations on DNA gyrase and topoisomerase IV by sequencing. Also 16 mutants had fluoroquinolones MICs that were 4-32 times lower in the presence of reserpine. In conclusion, alterations in DNA gyrase or topoisomerase IV and action of efflux pumping out system are the resistance mechanisms of DW-224a.

참고문헌 (Reference)

1 Dailidien, D., "Urea sensitization caused by separation of Helicobacter pylori RNA polymerase beta and beta' subunit" 12 (12): 103-, 2007

2 Florian, D. E., "Transcriptional profiles of Helicobacter pylori Fur- and iron regulated gene expression" 151 : 533-, 2005

3 Hall, H. K., "The role of Fur in the acid tolerance response of Salmonella typhimurium is physiologically separable from its role in iron acquisition" 178 : 5683-, 1996

4 Vasil, L. M., "The response of Pseudomonas aeruginosa to iron: genetics, biochemistry and virulence" 34 (34): 399-, 1999

5 Delany, I., "The Fur repressor controls transcription of iron-activated and -repressed genes in Helicobacter pylori" 42 : 1297-, 2001

6 Jeong, J. Y., "Sequential inactivation of rdxA (HP0954) and frxA (HP0642) nitroreductase genes cause moderate and high-level metronidazole resistance in Helicobacter pylori" 5082(2000) 182 (182): 5082-, 2000

7 Albert, D. T., "Mutational discovery in bacterial genomes: metronidazole resistance in Helicobacter pylori" 2 : 951-, 2005

8 Tan, S., "Motility of urease-deficient derivatives of Helicobacter pylori" 186 (186): 885-, 2004

9 Tourati, D., "Iron and oxidative stress in bacteria" 373 : 1-, 2000

10 Hanke, K., "Iron and metal regulation in bacteria" 4 : 172-, 2001

11 Vartanian, J. P., "Hypermutagenic PCR involving all four transition and a sizeable proportion of transversion" 24 : 2627-, 1996

12 Ramarao, N., "Helicobacter pylori induces but survives the extracellular release of oxygen radical from professional phagocytes using catalase activity" 38 : 103-, 2000

13 Blaser, M. J., "Helicobacter pylori genetic diversity and risk of human disease" 107 : 767-, 2001

14 Nardone, G., "Helicobacter pylori and molecular events in precancerous gastric lesions" 20 : 261-, 2004

15 Parsonnet, J., "Helicobacter and gastric adenocarcinoma, In Microbes and malignancy: Infection as a cause of human cancer" Oxford University Press 372-408, 1999

16 Dailidien, D., "Finding mutations implicated in Mtz hyperrsistance"

17 Bagg, A., "Ferric uptake regulation protein acts as a repressor, employing iron (II) as a cofactor to bind the operator of an iron transport operon in Escherichia coli" 26 : 5471-, 1987

18 Hazell, S. L., "Evasion of the toxic effects of oxygen. In Helicobacter pylori; physiology and genetics" American Society for Microbiology Press 167-175, 2001

19 Garry, S., "Enzymes associated with reductive activation and action of nitrozoxamide, nitrofurans, and metronidazole in Helicobacter pylori" 146 (146): 2116-, 2002

20 Westblom, J. U., "Current topics in microbiology and immunology, vol. 241, gastroduodenal disease and Helicobacter pylori: pathology, diagnosis and treatment" Springer Press

21 Peredo, A. G., "Conformational changes of the ferric uptake regulation protein upon metal activation and DNA binding; first evidence of structural homologies with the diphtheria toxin repressor" 310 : 83-, 2001

22 Israel, D. A., "Characteristics of Helicobacter pylori natural transformation" 186 : 275-, 2000

23 Andrew, S. C., "Bacterial iron homeostasis" 27 : 215-, 2003

24 Pohl, E., "Architecture of a protein central to iron homeostasis: crystal structure and spectroscopic analysis of the ferric uptake regulator" 47 (47): 903-, 2003