title: Antimicrobial susceptibility and resistance patterns among Helicobacter pylori strains from The Gambia, West Africa.
abstract: Helicobacter pylori is a globally important and genetically diverse gastric pathogen that infects most people in developing countries. Eradication efforts are complicated by antibiotic resistance, which varies in frequency geographically. There are very few data on resistance in African strains. Sixty-four Gambian H. pylori strains were tested for antibiotic susceptibility. The role of rdxA in metronidazole (Mtz) susceptibility was tested by DNA transformation and sequencing; RdxA protein variants were interpreted in terms of RdxA structure. Forty-four strains (69%) were resistant to at least 8 μg of Mtz/ml. All six strains from infants, but only 24% of strains from adults, were sensitive (P = 0.0031). Representative Mtz-resistant (Mtz(r)) strains were rendered Mtz susceptible (Mtz(s)) by transformation with a functional rdxA gene; conversely, Mtz(s) strains were rendered Mtz(r) by rdxA inactivation. Many mutations were found by Gambian H. pylori rdxA sequencing; mutations that probably inactivated rdxA in Mtz(r) strains were identified and explained using RdxA protein's structure. All of the strains were sensitive to clarithromycin and erythromycin. Amoxicillin and tetracycline resistance was rare. Sequence analysis indicated that most tetracycline resistance, when found, was not due to 16S rRNA gene mutations. These data suggest caution in the use of Mtz-based therapies in The Gambia. The increasing use of macrolides against respiratory infections in The Gambia calls for continued antibiotic susceptibility monitoring. The rich variety of rdxA mutations that we found will be useful in further structure-function studies of RdxA, the enzyme responsible for Mtz susceptibility in this important pathogen.
authors.affiliation: Medical Research Council Unit, Fajara, The Gambia. osecka@mrc.gm
authors.forename: Ousman
authors.initials: O
authors.lastname: Secka
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Berg
authors.forename: Martin
authors.initials: M
authors.lastname: Antonio
authors.forename: Tumani
authors.initials: T
authors.lastname: Corrah
authors.forename: Mary
authors.initials: M
authors.lastname: Tapgun
authors.forename: Robert
authors.initials: R
authors.lastname: Walton
authors.forename: Vivat
authors.initials: V
authors.lastname: Thomas
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Galano
authors.forename: Javier
authors.initials: J
authors.lastname: Sancho
authors.forename: Richard A
authors.initials: RA
authors.lastname: Adegbola
authors.forename: Julian E
authors.initials: JE
authors.lastname: Thomas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D017291:Clarithromycin / Q000494:pharmacology; D004252:DNA Mutational Analysis; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics*; D004917:Erythromycin / Q000494:pharmacology; D005260:Female; D005714:Gambia; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D008297:Male; D008795:Metronidazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D009601:Nitroreductases / Q000235:genetics*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D013752:Tetracycline / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012336:RNA, Ribosomal, 16S; D008795:Metronidazole; D004917:Erythromycin; D000658:Amoxicillin; D009601:Nitroreductases; C476646:RdxA protein, Helicobacter pylori; D013752:Tetracycline; D017291:Clarithromycin