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http://dx.doi.org/10.5352/JLS.2005.15.6.955

Biological Effect of Metronidazole Resistance in Helicobacter Pylori  

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)
Publication Information
Journal of Life Science / v.15, no.6, 2005 , pp. 955-960 More about this Journal
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.
Keywords
Helicobacter pylori; Metronidazole resistance; rdxA; frxA; nitroreductase genes.;
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