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http://dx.doi.org/10.5352/JLS.2007.17.5.723

Mechanism of Metronidazole Resistance Regulated by the fdxA Gene in Helicobacter pylori.  

Nam, Won-Hee (Asan Institute for Life Sciences, University of Ulsan College of Medicine)
Lee, Sun-Mi (Asan Institute for Life Sciences, University of Ulsan College of Medicine)
Kim, Eun-Sil (Asan Institute for Life Sciences, University of Ulsan College of Medicine)
Kim, Jin-Ho (Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine)
Jeong, Jin-Yong (Asan Institute for Life Sciences, University of Ulsan College of Medicine)
Publication Information
Journal of Life Science / v.17, no.5, 2007 , pp. 723-727 More about this Journal
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).
Keywords
fdxA; Helicobacter pylori; metronidazole resistance;
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