ArticleAntimicrobial agents and chemotherapy1999
RecA-Mediated gene conversion and aminoglycoside resistance in strains heterozygous for rRNA.
Article in Antimicrobial agents and chemotherapy, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 64 citations in OpenAlex.
- Key Proteins and Enzymatic Mechanisms Underlying Drug Resistance in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Evolutionary Pathways and Trajectories in Antibiotic Resistance.Clinical microbiology reviews · 2021Article
- Rates of gene conversions between Escherichia coli ribosomal operons.G3 (Bethesda, Md.) · 2021Article
- Identification of novel scaffolds targeting Mycobacterium tuberculosis.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Design, Multigram Synthesis, and in Vitro and in Vivo Evaluation of Propylamycin: A Semisynthetic 4,5-Deoxystreptamine Class Aminoglycoside for the Treatment of Drug-Resistant Enterobacteriaceae and Other Gram-Negative Pathogens.Journal of the American Chemical Society · 2019Article
- Ribosomal mutations promote the evolution of antibiotic resistance in a multidrug environment.eLife · 2017Article
- Public health evolutionary biology of antimicrobial resistance: priorities for intervention.Evolutionary applications · 2015Article
- In vivo efficacy of apramycin in murine infection models.Antimicrobial agents and chemotherapy · 2014Article
- Molecular basis for the selectivity of antituberculosis compounds capreomycin and viomycin.Antimicrobial agents and chemotherapy · 2011Article
- Article
- Homozygous triplicate mutations in three 16S rRNA genes responsible for high-level aminoglycoside resistance in Nocardia farcinica clinical isolates from a Canada-wide bovine mastitis epizootic.Antimicrobial agents and chemotherapy · 2010Article
- Influence of recombination on development of mutational resistance to linezolid in Enterococcus faecalis JH2-2.Antimicrobial agents and chemotherapy · 2009Article
- Genetic analysis of interactions with eukaryotic rRNA identify the mitoribosome as target in aminoglycoside ototoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Recombination and selection can remove blaTEM alleles from bacterial populations.Antimicrobial agents and chemotherapy · 2008Article
- Insights into the evolutionary history of tubercle bacilli as disclosed by genetic rearrangements within a PE_PGRS duplicated gene pair.BMC evolutionary biology · 2006Article
- Binding of neomycin-class aminoglycoside antibiotics to mutant ribosomes with alterations in the A site of 16S rRNA.Antimicrobial agents and chemotherapy · 2006Article
- Heterogeneous macrolide resistance and gene conversion in the pneumococcus.Antimicrobial agents and chemotherapy · 2006Article
- Analysis of the contribution of individual substituents in 4,6-aminoglycoside-ribosome interaction.Antimicrobial agents and chemotherapy · 2005Article
- Fitness cost due to mutations in the 16S rRNA associated with spectinomycin resistance in Chlamydia psittaci 6BC.Antimicrobial agents and chemotherapy · 2005Article
- Mutational analysis of 16S and 23S rRNA genes of Thermus thermophilus.Journal of bacteriology · 2005Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clinical resistance to aminoglycosides in general is due to enzymatic drug modification. Mutational alterations of the small ribosomal subunit rRNA have recently been found to mediate acquired resistance in bacterial pathogens in vivo. In this study we investigated the effect of 16S rRNA heterozygosity (wild-type [wt] and mutant [mut] operons at position 1408 [1408wt/1408mut]) on aminoglycoside resistance. Using an integrative vector, we introduced a single copy of a mutated rRNA operon (1408 A-->G) into Mycobacterium smegmatis, which carries two chromosomal wild-type rRNA operons; the resultant transformants exhibited an aminoglycoside-sensitive phenotype. In contrast, introduction of the mutated rRNA operon into an M. smegmatis rrnB knockout strain carrying a single functional chromosomal wild-type rRNA operon resulted in aminoglycoside-resistant transformants. Subsequent analysis by DNA sequencing and RNase protection assays unexpectedly demonstrated a homozygous mutant genotype, rRNAmut/rRNAmut, in the resistant transformants. To investigate whether RecA-mediated gene conversion was responsible for the aminoglycoside-resistant phenotype in the rRNAwt/rRNAmut strains, recA mutant strains were generated by allelic exchange techniques. Transformation of the recA rrnB M. smegmatis mutant strains with an integrative vector expressing a mutated rRNA operon (Escherichia coli position 1408 A-->G) resulted in transformants with an aminoglycoside-sensitive phenotype. Subsequent analysis showed stable heterozygosity at 16S rRNA position 1408 with a single wild-type allele and a single resistant allele. These results demonstrate that rRNA-mediated mutational resistance to aminoglycosides is recessive.
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