Cited by 101Helicobacter pylori-related gastroenterology studiesAntibiotic Resistance in BacteriaBacterial Genetics and Biotechnology

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Emergence of Tetracycline Resistance in Helicobacter pylori : Multiple Mutational Changes in 16S Ribosomal DNA and Other Genetic Loci

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Dailidiene, Daiva, Bertoli, M. Teresita, Miciuleviciene, Jolanta, Mukhopadhyay, Asish K., Dailide, Giedrius, Pascasio, Mario Alberto, Kupcinskas, Limas, Berg, Douglas E.·2002·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.46.12.3940-3946.2002PMC PMC132778

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Abstract

Tetracycline is useful in combination therapies against the gastric pathogen Helicobacter pylori . We found 6 tetracycline-resistant (Tet r ) strains among 159 clinical isolates (from El Salvador, Lithuania, and India) and obtained the following four results: (i) 5 of 6 Tet r isolates contained one or two nucleotide substitutions in one part of the primary tetracycline binding site in 16S rRNA (AGA 965-967 [ Escherichia coli coordinates] changed to gGA, AGc, guA, or gGc [lowercase letters are used to represent the base changes]), whereas the sixth (isolate Ind75) retained AGA 965-967 ; (ii) PCR products containing mutant 16S ribosomal DNA (rDNA) alleles transformed recipient strains to Tet r phenotypes, but transformants containing alleles with single substitutions (gGA and AGc) were less resistant than their Tet r parents; (iii) each of 10 Tet r mutants of reference strain 26695 (in which mutations were induced with metronidazole, a mutagenic anti- H. pylori agent) contained the normal AGA 965-967 sequence; and (iv) transformant derivatives of Ind75 and of one of the Tet r 26695 mutants that had acquired mutant rDNA alleles were resistant to tetracycline at levels higher than those to which either parent strain was resistant. Thus, tetracycline resistance in H. pylori results from an accumulation of changes that may affect tetracycline-ribosome affinity and/or other functions (perhaps porins or efflux pumps). We suggest that the rarity of tetracycline resistance among clinical isolates reflects this need for multiple mutations and perhaps also the deleterious effects of such mutations on fitness. Formally equivalent mutations with small but additive effects are postulated to contribute importantly to traits such as host specificity and virulence and to H. pylori 's great genetic diversity.

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Authors: Dailidiene, D., Bertoli, M. T., Miciuleviciene, J., Mukhopadhyay, A. K., Dailide, G., Pascasio, M. A., Kupcinskas, L., & Berg, D. E.
Affiliations: Washington University in St. Louis (US)
Departments of Molecular Microbiology and Genetics, Washington University Medical School, St. Louis, Missouri 63110
Ministerio de Salud (SV)
Department of Gastroenterology, Kaunas University of Medicine, Kaunas, 3000, Lithuania
ORCID: Mukhopadhyay, Asish K.
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 2002-12
Volume: 46
Issue: 12
Pages: 3940-3946
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.46.12.3940-3946.2002
PMC: PMC132778
OpenAlex: W2153045047
Cited by: 101
References: 50
Citations by year: 2026: 2 · 2025: 7 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 8 · 2015: 5 · 2014: 7 · 2013: 1 · 2012: 4
FWCI: 7.00
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Lithuanian University of Health Sciences (submittedVersion)
Funders: National Institutes of Health (2r01ai038166-04, 1r03ai049161-01, 5r01dk053727-04)
U.S. Public Health Service
National Institute of Allergy and Infectious Diseases (AI49161, AI 38166)
National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK-52574, DK53727, P30DK052574)
Topics: Health Sciences › Medicine › Gastroenterology › Helicobacter pylori-related gastroenterology studies
Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords: Helicobacter pylori, tetracycline resistance, 16S rRNA mutations, multiple mutations, antibiotic resistance mechanisms, efflux pumps, porin, clinical isolates, genetic diversity
MeSH terms: Cells, Cultured, Mutation, RNA, Ribosomal, 16S, Tetracycline Resistance, Polymerase Chain Reaction, Helicobacter pylori

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Emergence of Tetracycline Resistance in Helicobacter pylori : Multiple Mutational Changes in 16S Ribosomal DNA and Other Genetic Loci

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