Molecular analysis of tlrB, an antibiotic-resistance gene from tylosin-producing Streptomyces fradiae, and discovery of a novel resistance mechanism

J Antibiot (Tokyo). 1999 Mar;52(3):288-96. doi: 10.7164/antibiotics.52.288.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Amino Acid Sequence
  • Anti-Bacterial Agents / biosynthesis*
  • Anti-Bacterial Agents / chemistry
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Carrier Proteins / genetics
  • Colony Count, Microbial
  • DNA, Bacterial / analysis
  • DNA, Bacterial / genetics
  • Drug Resistance, Microbial
  • Escherichia coli Proteins*
  • Fermentation
  • Genes, Bacterial*
  • Genome
  • Maltose-Binding Proteins
  • Methyltransferases / metabolism
  • Molecular Sequence Data
  • Monosaccharide Transport Proteins*
  • Periplasmic Binding Proteins*
  • Phenotype
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Streptomyces / enzymology
  • Streptomyces / genetics
  • Streptomyces / metabolism*
  • Tylosin / biosynthesis*
  • Tylosin / chemistry

Substances

  • ATP-Binding Cassette Transporters
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carrier Proteins
  • DNA, Bacterial
  • Escherichia coli Proteins
  • MalE protein, E coli
  • Maltose-Binding Proteins
  • Monosaccharide Transport Proteins
  • Periplasmic Binding Proteins
  • Recombinant Fusion Proteins
  • maltose transport system, E coli
  • Methyltransferases
  • TlrB protein, Streptomyces fradiae
  • Tylosin

Associated data

  • GENBANK/AJ009971