Mutations of the Helicobacter pylori genes rdxA and pbp1 cause resistance against metronidazole and amoxicillin

Abstract

To investigate amoxicillin and metronidazole resistance of Helicobacter pylori, we compared putative resistance genes between resistant strains obtained in vitro and their sensitive parent strain. All metronidazole-resistant strains had rdxA mutations, and an amoxicillin-resistant strain had pbp1 and pbp2 mutations. By transforming PCR products of these mutated genes into antibiotic-sensitive strains, we showed that rdxA null mutations were sufficient for metronidazole resistance, while pbp1 mutations contributed to amoxicillin resistance of H. pylori.

FIG. 1

Alignment of RdxA proteins from H. pylori 69A strains selected for antibiotic resistance (A) and those of H. pylori wild-type strains (B). (A) The strains 69A and 69A/Amx^r were metronidazole sensitive, and the 69A/Mtz^r1 to -5 strains were metronidazole resistant. (B) H. pylori strains 26695, 503, 69A, and 500 were metronidazole sensitive, and H. pylori strains 439 and 504 (ATCC 43504) were metronidazole resistant. A black background shows the conservation of amino acid residues. H. pylori amino acid sequences are given as follows: 26695, reference ; strains 500 and 439, reference ; strain 503, GenBank accession no. AF316109; strain 504, accession no. AF315501; and strain 69A, accession no. AF315502.