title: Deglycosylation as a mechanism of inducible antibiotic resistance revealed using a global relational tree for one-component regulators.
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.
authors: Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada.
authors: Leslie
authors: L
authors: Cuthbertson
authors: Sang Kyun
authors: SK
authors: Ahn
authors: Justin R
authors: JR
authors: Nodwell
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001105:Archaea / Q000145:classification / Q000378:metabolism; D001419:Bacteria / Q000145:classification / Q000187:drug effects / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D006031:Glycosylation; D008024:Ligands; D010802:Phylogeny; D013752:Tetracycline / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008024:Ligands; D014157:Transcription Factors; C033276:kijanimicin; D004247:DNA; D013752:Tetracycline