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KMID : 0613820070170050723
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Journal of Life Science
2007 Volume.17 No. 5 p.723 ~ p.727
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Mechanism of Metronidazole Resistance Regulated by the fdxA Gene in Helicobacter pylori
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Nam Won-Hee
Lee Sun-Mi
Kim Eun-Sil
Kim Jin-Ho
Jeong Jin-Yong
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Abstract
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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 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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KEYWORD
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fdxA, Helicobacter pylori, metronidazole resistance
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