The rdxA gene plays a more major role than frxA gene mutation in high-level metronidazole resistance of Helicobacter pylori in Taiwan.
BACKGROUND
Metronidazole-resistant H. pylori associating with mutations of rdxA or frxA is still a debated topic. This study investigates whether rdxA and frxA mutations of H. pylori accounted for the high MIC value (>/= 64 micro g/ml) of metronidazole (Mtz).


METHODS
From 126 clinical H. pylori isolates, we examined 14 Mtz-sensitive, 18 Mtz-resistant H. pylori, and eight pairs of Mtz-sensitive and Mtz-resistant colonies simultaneously present within a single gastric biopsy. The paired strains from one single biopsy were proven identical by PCR-RFLP. MICs of Mtz were checked by the E-test and agar dilution method. The mutations of rdxA and frxA sequencing were matched with the Mtz-susceptible ATCC 26695 and J99.


RESULTS
There were 89% (16/18) of Mtz-resistant isolates with mutation of RdxA. Half of the 14 Mtz-sensitive strains, all without mutation of RdxA, still contained truncation of FrxA. Within the paired isolates from a single biopsy, rdxA mutation (86%) was more common than frxA mutation (43%) in those isolates with high-level Mtz-resistant H. pylori. RdxA truncation was more prevalent in Mtz-resistant strains with high MICs than in those with low to moderate MICs (75% vs. 20%, p =.01, OR: 12, 95% CI: 1.8-81.7).


CONCLUSIONS
Mutations in the rdxA gene rather than the frxA gene generally determine a high MIC level of Mtz-resistant H. pylori in Taiwan.
Yang
Yao-Jong
YJ
Department of Pediatrics, Medical College, National Cheng Kung University, Tainan, Taiwan.
Wu
Jiunn-Jong
JJ
Sheu
Bor-Shyang
BS
Kao
Ai-Wen
AW
Huang
Ay-Huey
AH
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D001706:Biopsy; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008795:Metronidazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D009601:Nitroreductases / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D016415:Sequence Alignment; D013624:Taiwan
D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D008795:Metronidazole; D010088:Oxidoreductases; D009601:Nitroreductases; C476646:RdxA protein, Helicobacter pylori