A response regulator from a soil metagenome enhances resistance to the β-lactam antibiotic carbenicillin in Escherichia coli

PloS One
Heather K AllenLuke A Moe

Abstract

Functional metagenomic analysis of soil metagenomes is a method for uncovering as-yet unidentified mechanisms for antibiotic resistance. Here we report an unconventional mode by which a response regulator derived from a soil metagenome confers resistance to the β-lactam antibiotic carbenicillin in Escherichia coli. A recombinant clone (βlr16) harboring a 5,169 bp DNA insert was selected from a metagenomic library previously constructed from a remote Alaskan soil. The βlr16 clone conferred specific resistance to carbenicillin, with limited increases in resistance to other tested antibiotics, including other β-lactams (penicillins and cephalosporins), rifampin, ciprofloxacin, erythromycin, chloramphenicol, nalidixic acid, fusidic acid, and gentamicin. Resistance was more pronounced at 24°C than at 37°C. Zone-of-inhibition assays suggested that the mechanism of carbenicillin resistance was not due to antibiotic inactivation. The DNA insert did not encode any genes known to confer antibiotic resistance, but did have two putative open reading frames (ORFs) that were annotated as a metallopeptidase and a two-component response regulator. Transposon mutagenesis and subcloning of the two ORFs followed by phenotypic assays showed that t...Continue Reading

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Citations

May 23, 2015·Biotechnology Letters·Débora Farage Knupp dos SantosRicardo Henrique Krüger
Oct 7, 2016·Microbial Ecology·Débora Farage Knupp Dos SantosRicardo Henrique Kruger
Jan 13, 2017·Database : the Journal of Biological Databases and Curation·James C WallaceElaine M Faustman
Feb 6, 2021·The Science of the Total Environment·Xi-Ran WangJian Sun

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Datasets Mentioned

BETA
EU408353.1

Methods Mentioned

BETA
PCR
PCRs
gene knockouts

Software Mentioned

Basic Local Alignment Search Tool ( BLAST )
DNASTAR
Lasergene
MegAlign
blastP

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