Frequent association between alteration of the rdxA gene and metronidazoleresistance in French and North African isolates of Helicobacter pylori

Mutations in the rdxA gene have been associated with the acquisition of res istance to metronidazole in Helicobacter pylori, This gene encodes an NADPH nitroreductase whose expression is necessary for intracellular activation of the drug. We wished to examine whether mutations in rdxA were present in resistant H. pylori isolates infecting either French or North African pati ents, We determined the complete nucleotide sequences of the rdxA genes fro m seven French and six North African patients infected with paired resistan t and sensitive strains. Genotyping by random amplified polymorphic DNA ana lysis confirmed the close genetic relatedness of the susceptible and resist ant isolates from individual biopsies. Eight French and five North African individual resistant strains were also studied. For the French strains, an alteration in rdxA most probably implicated in resistance was found in 10 c ases (seven frameshift mutations, two missense mutations, and one deletion of 211 bp). One to three putative missense mutations were identified in fou r cases, and a missense mutation possibly not implicated in resistance was discovered in the last case. For the North African strains, an alteration i n rdxA was found in eight cases (three frameshift mutations, three missense mutations, one deletion of 6 bp, and one insertion of a variant of IS605). Two strains contained putative missense mutations, and no change was obser ved in rdxA of the last strain, Thus, inactivation of the rdxA gene is freq uently, but not always, associated with resistance to metronidazole in Fren ch and North African clinical isolates of H. pylori. In addition, a variety of alterations of rdxA are associated with the resistant phenotype.