Functional metagenomic approach to identify overlooked antibiotic resistance mutations in bacterial rRNA

書誌事項

公開日
2018-04-03
権利情報
  • https://creativecommons.org/licenses/by/4.0
  • https://creativecommons.org/licenses/by/4.0
DOI
  • 10.1038/s41598-018-23474-4
公開者
Springer Science and Business Media LLC

説明

<jats:title>Abstract</jats:title> <jats:p> Our knowledge as to how bacteria acquire antibiotic resistance is still fragmented, especially for the ribosome-targeting drugs. In this study, with the aim of finding novel mechanisms that render bacteria resistant to the ribosome-targeting antibiotics, we developed a general method to systematically screen for antibiotic resistant 16 S ribosomal RNAs (rRNAs), which are the major target for multiple antibiotics (e.g. spectinomycin, tetracycline, and aminoglycosides), and identify point mutations therein. We used <jats:italic>Escherichia coli</jats:italic> ∆7, a null mutant of the <jats:italic>rrn</jats:italic> (ribosomal RNA) operons, as a surrogate host organism to construct a metagenomic library of 16 S rRNA genes from the natural (non-clinical) environment. The library was screened for spectinomycin resistance to obtain four resistant 16 S rRNA genes from non- <jats:italic>E. coli</jats:italic> bacterial species. Bioinformatic analysis and site-directed mutagenesis identified three novel mutations - U1183C (the first mutation discovered in a region other than helix 34), and C1063U and U1189C in helix 34 - as well as three well-described mutations (C1066U, C1192G, and G1193A). These results strongly suggest that uncharacterized antibiotic resistance mutations still exist, even for traditional antibiotics. </jats:p>

収録刊行物

  • Scientific Reports

    Scientific Reports 8 (1), 5179-, 2018-04-03

    Springer Science and Business Media LLC

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