Deglycosylation as a Mechanism of Inducible Antibiotic Resistance Revealed Using a Global Relational Tree for One-Component Regulators

SummaryThe 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.

Graphical AbstractFigure optionsDownload high-quality image (97 K)Download as PowerPoint slideHighlights
► Phylogenomics can be used to predict cognate ligands for TetR-family regulators
► KijR (SCO7719) regulates kijX (SCO7720) in response to the antibiotic kijanimicin
► kijX encodes a kijanimicin-resistance determinant
► KijX is a glycosyl hydrolase and inactivates kijanimicin through deglycosylation