Molecular analysis of tlrB, an antibiotic-resistance gene from tylosin-producing Streptomyces fradiae, and discovery of a novel resistance mechanism.
The tlrB gene, which confers inducible resistance to a range of macrolide antibiotics including biosynthetic precursors of tylosin, was isolated and sequenced. In the genome of Streptomyces fradiae, it lies between pbp, which encodes a putative penicillin-binding protein, and tylN, encoding a glycosyltransferase involved in tylosin biosynthesis. The TlrB protein was produced in E. coli as a fusion to MalE. The fusion protein, but not MalE alone, inactivates macrolides in the presence of S-adenosyl-methionine (SAM) but the modified product(s) has not been characterised.
Wilson
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Department of Biochemistry, University of Leicester, UK.
Cundliffe
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D018528:ATP-Binding Cassette Transporters; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D015169:Colony Count, Microbial; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D004352:Drug Resistance, Microbial; D029968:Escherichia coli Proteins; D005285:Fermentation; D005798:Genes, Bacterial; D016678:Genome; D058619:Maltose-Binding Proteins; D008780:Methyltransferases / Q000378:metabolism; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins; D033902:Periplasmic Binding Proteins; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D015645:Tylosin / Q000096:biosynthesis* / Q000737:chemistry
D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C461619:MalE protein, E coli; D058619:Maltose-Binding Proteins; D009004:Monosaccharide Transport Proteins; D033902:Periplasmic Binding Proteins; D011993:Recombinant Fusion Proteins; C461599:maltose transport system, E coli; D008780:Methyltransferases; C119401:TlrB protein, Streptomyces fradiae; D015645:Tylosin