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      헬리코박터 파일로리에서 fdxA 유전자에 의한 메트로니다졸 내성 조절 기전 연구 = Mechanism of Metronidazole Resistance Regulated by the fdxA Gene in Helicobacter pylori.

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      https://www.riss.kr/link?id=A103756200

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      다국어 초록 (Multilingual Abstract)

      Resistance to metronidazole in Helicobacter pylori results from inactivation of rdxA and frxA, the chromosomal genes for a nitroreductase that normally converts metronidazole from prodrug to bactericidal agent. Two types of metronidazole susceptible strains had been found distinguishable by their apparent levels of frxA expression. Most common in the populations we had studied were strains that required only rdxA inactivation to become resistant to moderate levels of metronidazole(type I strains). The second strain type required inactivation of both frxA and rdxA to become resistance to metronidazole(type II strains): this was linked to a relatively high level of frxA gene transcription in the type II strains. The fdxA gene regulated fdxA as well as rdxA gene. Thus, to study the function of fdxA as a regulatory gene we constructed a null mutant of fdxA in H. pylori genome and identified over-and under-expressed proteins by fdxA using two-dimensional(2-D) electrophoresis and MALDI-TOP-MS. There were four over-expressed proteins in fdxA mutant; nifU-like protein(HP0221), frxA(HP0642), nonheme ferritin(HP0653), and hypothetical protein(HP0902). Three under-expressed proteins were also identified in fdxA mutant, including 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (HP0089), (3R)-hydroxymyristoyl ACP dehydratase(HP1376), and thioredoxin(HP1458).
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      Resistance to metronidazole in Helicobacter pylori results from inactivation of rdxA and frxA, the chromosomal genes for a nitroreductase that normally converts metronidazole from prodrug to bactericidal agent. Two types of metronidazole susceptible s...

      Resistance to metronidazole in Helicobacter pylori results from inactivation of rdxA and frxA, the chromosomal genes for a nitroreductase that normally converts metronidazole from prodrug to bactericidal agent. Two types of metronidazole susceptible strains had been found distinguishable by their apparent levels of frxA expression. Most common in the populations we had studied were strains that required only rdxA inactivation to become resistant to moderate levels of metronidazole(type I strains). The second strain type required inactivation of both frxA and rdxA to become resistance to metronidazole(type II strains): this was linked to a relatively high level of frxA gene transcription in the type II strains. The fdxA gene regulated fdxA as well as rdxA gene. Thus, to study the function of fdxA as a regulatory gene we constructed a null mutant of fdxA in H. pylori genome and identified over-and under-expressed proteins by fdxA using two-dimensional(2-D) electrophoresis and MALDI-TOP-MS. There were four over-expressed proteins in fdxA mutant; nifU-like protein(HP0221), frxA(HP0642), nonheme ferritin(HP0653), and hypothetical protein(HP0902). Three under-expressed proteins were also identified in fdxA mutant, including 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (HP0089), (3R)-hydroxymyristoyl ACP dehydratase(HP1376), and thioredoxin(HP1458).

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      참고문헌 (Reference)

      1 Mukhopadhyay, A. K, "The fdxA ferredoxin gene can down-regulate frxA nitroreductase gene expression and is essential in many strains of Helicobacter pylori" 185 : 2927-2935, 2003

      2 Tomb, J. F., "The complete genome sequence of the gastric pathogen Helicobacter pylori" 388 : 539-547, 1997

      3 Jeong, J. Y., "Sequential inactivation of rdxA (HP0954) and frxA (HP0642) nitroreductase genes cause moderate and high- level metronidazole resistance in Helicobacter pylori" 182 : 5082-5090, 2000

      4 Jeong, J. Y., "Roles of FrxA and RdxA nitroreductases of Helicobacter pylori in susceptibility and resistance to metronidazole" 183 : 5155-5162, 2001

      5 Lingwood, C. A., "Receptor affinity purification of a lipid-binding adhesin from Helicobacter pylori" 61 : 2474-2478, 1993

      6 Rhee, K. H., "Prevalence of Helicobacter pylori Infection in Korea" 25 : 475-490, 1990

      7 Edwards, D. I., "Nitroimidazole drugs-action and resistance mechanisms. II. Mechanisms of resistance" 31 : 201-210, 1993

      8 Jeong, J. Y, "Mouse-colonizing Helicobacter pylori SS1 is unusually susceptible to metronidazole due to two complementary reductase activities" 44 : 3127-3132, 2000

      9 Chiba, N., "Meta-analysis of the efficacy of antibiotic therapy in eradicating Helicobacter pylori" 87 : 1716-1727, 1992

      10 Isaacson, P. G., "Is gastric lymphoma an infectious disease?" 24 : 569-570, 1993

      1 Mukhopadhyay, A. K, "The fdxA ferredoxin gene can down-regulate frxA nitroreductase gene expression and is essential in many strains of Helicobacter pylori" 185 : 2927-2935, 2003

      2 Tomb, J. F., "The complete genome sequence of the gastric pathogen Helicobacter pylori" 388 : 539-547, 1997

      3 Jeong, J. Y., "Sequential inactivation of rdxA (HP0954) and frxA (HP0642) nitroreductase genes cause moderate and high- level metronidazole resistance in Helicobacter pylori" 182 : 5082-5090, 2000

      4 Jeong, J. Y., "Roles of FrxA and RdxA nitroreductases of Helicobacter pylori in susceptibility and resistance to metronidazole" 183 : 5155-5162, 2001

      5 Lingwood, C. A., "Receptor affinity purification of a lipid-binding adhesin from Helicobacter pylori" 61 : 2474-2478, 1993

      6 Rhee, K. H., "Prevalence of Helicobacter pylori Infection in Korea" 25 : 475-490, 1990

      7 Edwards, D. I., "Nitroimidazole drugs-action and resistance mechanisms. II. Mechanisms of resistance" 31 : 201-210, 1993

      8 Jeong, J. Y, "Mouse-colonizing Helicobacter pylori SS1 is unusually susceptible to metronidazole due to two complementary reductase activities" 44 : 3127-3132, 2000

      9 Chiba, N., "Meta-analysis of the efficacy of antibiotic therapy in eradicating Helicobacter pylori" 87 : 1716-1727, 1992

      10 Isaacson, P. G., "Is gastric lymphoma an infectious disease?" 24 : 569-570, 1993

      11 Knipp, U., "Immune suppressive effects of Helicobacter pylori on human peripheral blood mononuclear cells" 182 : 63-76, 1993

      12 Malaty, H. M., "Helicobacter pylori infection: genetic and environmental influences" 120 : 982-986, 1994

      13 Graham, D. Y., "Helicobacter pylori infection in the pathogenesis of duodenal ulcer and gastric cancer: a model" 113 : 1983-1991, 1997

      14 Moss, S., "Helicobacter pylori and peptic ulcers: the present position" 33 : 289-292, 1992

      15 Graham, D. Y., "H. pylori and cagA: relationships with gastric cancer, duodenal ulcer, and reflux esophagitis and its complications" 3 : 145-151, 1998

      16 Wotherspoon, A. C, "Gastric MALT lymphoma and Helicobacter pylori" 69 : 61-68,

      17 Harris, A., "Current regimens for treatment of Helicobacter pylori infection" 54 : 195-205, 1998

      18 Goodwin, C. S., "Campylobacter pyloridis, gastritis, and peptic ulceration" 39 : 353-365, 1986

      19 Andersen, L. P., "Campylobacter pyloridis in peptic ulcer disease. I. Gastric and duodenal infection caused by C. pyloridis: histopathologic and microbiologic findings" 22 : 219-224, 1987

      20 Kwon, D. H., "Analysis of rdxA and involvement of additional genes encoding NAD(P)H flavin oxidoreductase (FrxA) and ferredoxin-like protein (FdxB) in metronidazole resistance of Helicobacter pylori" 44 : 2133-2142,

      21 Kim, J. J., "Analysis of metronidazole, clarithromycin and tetracycline resistance of Helicobacter pylori isolates from Korea" 47 : 459-461, 2001

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      2027 평가예정 재인증평가 신청대상 (재인증)
      2021-01-01 평가 등재학술지 유지 (재인증) KCI등재
      2018-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2015-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2011-08-03 학술지명변경 외국어명 : Korean Journal of Life Science -> Journal of Life Science KCI등재
      2011-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2009-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2007-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2004-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2003-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2001-07-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 0.37 0.37 0.42
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.43 0.43 0.774 0.09
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