Alterations in rdxA and frxA genes and their upstream regions in metronidazole-resistant Helicobacter pylori isolates.
Metronidazole resistance among Helicobacter pylori strains has been related to alterations in gene products having metronidazole nitroreductase activities. RdxA and FrxA proteins are the two major contributing factors. In this investigation, the rdxA and frxA genes and their upstream regions were analyzed in 19 H. pylori isolates, 8 of which were metronidazole-sensitive (MIC < or = 8 microg/mL) and 11 of which were metronidazole-resistant (MIC > or = 8 microg/mL), as determined by the E-test. Among the metronidazole-resistant isolates, three contained both RdxA and FrxA proteins with premature truncation caused by gene nonsense mutations or frameshift mutations, while three contained only stop mutations in FrxA and two only in RdxA. Substitutions of amino acids occurred in other RdxA (5/6) and FrxA (4/5) proteins from metronidazole resistant isolates as compared with those from metronidazole-sensitive ones. All metronidazole-resistant isolates had alterations in RdxA and/or FrxA proteins. Moreover, the upstream regions (-1 to -35) of rdxA and frxA genes in some metronidazole-resistant isolates varied by nucleotide insertion and/or deletion or substitution. The patterns of variation in both genes and their upstream regions were highly diversified. Alterations in rdxA and frxA genes and their upstream regions may be involved in the development of metronidazole resistance in H. pylori.
Han
Fengchan
F
Institute of Genetic Diagnosis, State Key Laboratory of Cancer Biology, Faculty of Pharmacy, The Fourth Military Medical University, 17 West Changle Road, Xi'an 710032, Shaan'xi, China. fengchan@fmmu.edu.cn
Liu
Sookyin
S
Ho
Bow
B
Yan
Zhen
Z
Yan
Xiaojun
X
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D014644:Genetic Variation; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008795:Metronidazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D016415:Sequence Alignment
D000890:Anti-Infective Agents; D008795:Metronidazole