title: Tetracycline-resistant clinical Helicobacter pylori isolates with and without mutations in 16S rRNA-encoding genes.
abstract: Tetracycline-resistant Helicobacter pylori strains have been increasingly reported worldwide. However, only a small number of tetracycline-resistant strains have been studied with regard to possible mechanisms of resistance and those studies have focused on mutations in the tetracycline binding sites of 16S rRNA-encoding genes. We here report studies of 41 tetracycline-resistant H. pylori strains (tetracycline MICs, 4 to 32 microg/ml) from North America (n = 12) and from East Asia (n = 29). DNA sequence analyses of 16S rRNA-encoding genes revealed that 22 (54%) of the resistant isolates carried one of five different single-nucleotide substitutions (CGA, GGA, TGA, AGC, or AGT) at the putative tetracycline binding site (AGA(965-967)). Single-nucleotide substitutions were associated with reduced ribosomal binding and with slightly increased tetracycline MICs (1 to 2 microg/ml). The 19 tetracycline-resistant isolates with no detectable mutations in the tetracycline binding site had normal tetracycline-ribosome binding. All tetracycline-resistant isolates, including those with and those without mutations in the tetracycline binding site, showed decreased accumulation of tetracycline. These results suggest that tetracycline resistance is multifactorial, involving alterations both in ribosomal binding and in membrane permeability.
authors.affiliation: Veterans Affairs Medical Center and Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Jeng Yih
authors.initials: JY
authors.lastname: Wu
authors.forename: Jae J
authors.initials: JJ
authors.lastname: Kim
authors.forename: Rita
authors.initials: R
authors.lastname: Reddy
authors.forename: W M
authors.initials: WM
authors.lastname: Wang
authors.forename: David Y
authors.initials: DY
authors.lastname: Graham
authors.forename: Dong H
authors.initials: DH
authors.lastname: Kwon
mesh_terms: D017920:Antiporters / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D001665:Binding Sites; D002463:Cell Membrane Permeability / Q000187:drug effects; D004269:DNA, Bacterial / Q000235:genetics; D005838:Genotype; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics*; D012329:RNA, Bacterial / Q000235:genetics*; D012336:RNA, Ribosomal, 16S / Q000235:genetics*; D013753:Tetracycline Resistance / Q000235:genetics*; D013754:Tetracyclines / Q000378:metabolism
chemical_list: D017920:Antiporters; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; D013754:Tetracyclines; C079051:tetA protein, Bacteria