Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Biological Effect of Metronidazole Resistance in Helicobacter Pylori

Helicobacter pylori에서 metronidazole 내성이 미치는 생물학적 영향

  • Lee Gin Hyug (Division of Gastroenterology, Department of Internal Medicine, Asan Medical Center, Univeristy of Ulsan College of Medicine) ;
  • Lee Sun-Mi (Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Nam Won-Hee (Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim Eun Sil (Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim Jin Ho (Division of Gastroenterology, Department of Internal Medicine, Asan Medical Center, Univeristy of Ulsan College of Medicine) ;
  • Kang Ho Young (Department of Microbiology, Pusan National University) ;
  • Jeong Jin-Yong (Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine)
  • 이진혁 (울산대학교 의과대학 서울아산병원 소화기내과) ;
  • 이선미 (울산대학교 의과대학 아산생명과학연구소) ;
  • 남원희 (울산대학교 의과대학 아산생명과학연구소) ;
  • 김은실 (울산대학교 의과대학 아산생명과학연구소) ;
  • 김진호 (울산대학교 의과대학 서울아산병원 소화기내과) ;
  • 강호영 (부산대학교 생명과학부) ;
  • 정진용 (울산대학교 의과대학 아산생명과학연구소)
  • Published : 2005.12.01
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Abstract

Resistance to metronidazole, a key component of therapies against Helicobacter pylori, is common in clinical isolates. Resistance generally requires inactivation of rdxA (HP0954), and sometimes also frxA (HP0642), two related nitroreductase genes. Here we studied the effect of resistance to metronidazole on fitness of the gastric pathogen H. pylori. The effect of metronidazole resistance for H. pylori in culture was assessed first by looking at colonies formed by freshly constructed mutant derivatives of H. pylori strain 26695. Mutations resulting in metronidazole resistance caused premature death of H.pylori in stationary phase, but had no significant effect on early exponential growth. The effect of nitroreductase deficiencies on fitness in vivo was tested by infecting C57BL/6 mice with 1:1 mixtures of SS1 wild type and its isogenic metronidazole resistant derivatives. Inactivation of rdxA caused an inability to colonize mice in SS1 H. pylori strain. Derivatives of a metronidazole resistant strain that survived better in stationary phase, although remaining metronidazole resistant, could again colonize mice. In conclusion, metronidazole resistance diminishes H. pylori's fitness, but their costs can be suppressed by additional mutation.

메트로니다졸은 인체 위장질환의 원인균인 헬리코박터 파일로리를 박별하기위해 처방하는 주요 약제이다 그러나 인체로부터 분리한 헬리코박터 파일로리 균주는 메트로니다졸에 내성을 가지는 경우가 일반적이며, 이러한 내성원인은 이 균주의 염색체 상에 존재하는 두 종류의 nitroreductase 유전자인 rdxA와frxA 유전자가 비활성화됨에 따라 유발된다. 본 연구에서는 헬리코박터 파일로리 균에서 rdxA 유전자에 변이를 도입하여 메트로니다졸에 내성을 가지는 균주를 구축하여, 메트로니다졸 내성이 균주에 미치는 생물학적 영향을 관찰하고자 하였다. In vitro상에서 메트로니다졸 내성균주는 대조균과 비교하여 exponential phase에서는 거의 차이 없이 증식하였으나 stationary phase에서는 빠르게 생육활성을 잃는 것을 관찰할 수 있었다. 또한 생쥐를 이용한 동물 실험에서 메트로니다졸 내성균주는 생쥐의 위장 내에서 서식하는 능력을 상실함을 알 수 있었다. 그러나 이러한 생육 활성을 회복시켜주는 compensate템 mutation을 가진 균주를 쉽게 얻을 수 있었으며 이 균주는 생쥐에 감염시키면 위장 내에서 서식하는 능력을 회복함을 알 수 있었다.

Keywords

References

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