Deglycosylation as a mechanism of inducible antibiotic resistance revealed using a global relational tree for one-component regulators

Chem Biol. 2013 Feb 21;20(2):232-40. doi: 10.1016/j.chembiol.2012.11.011.

Abstract

The ligands that interact with the vast majority of small-molecule binding transcription factors are unknown, a significant gap in our understanding of sensory perception by cells. TetR-family regulators (TFRs) are found in most prokaryotes and are involved in regulating virtually every aspect of prokaryotic life however only a few TFRs have been characterized. We report the application of phylogenomics to the identification of cognate ligands for TFRs. Using phylogenomics we identify a TFR, KijR, that responds to the antibiotic kijanimicin. We go on to show that KijR represses a gene, kijX, which confers resistance to kijanimicin. Finally we show that KijX inactivates kijanimicin by the hydrolytic removal of sugar residues. This is a demonstration of antibiotic resistance by deglycosylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides / pharmacology*
  • Anti-Bacterial Agents / pharmacology*
  • Archaea / classification
  • Archaea / metabolism
  • Bacteria / classification
  • Bacteria / drug effects
  • Bacteria / metabolism
  • Bacterial Proteins / metabolism
  • DNA / metabolism
  • Drug Resistance, Bacterial / drug effects*
  • Glycosylation
  • Ligands
  • Phylogeny
  • Tetracycline / pharmacology*
  • Transcription Factors / metabolism

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Ligands
  • Transcription Factors
  • kijanimicin
  • DNA
  • Tetracycline