Structural basis of a histidine-DNA nicking/joining mechanism for gene transfer and promiscuous spread of antibiotic resistance.
Radoslaw PlutaD Roeland BoerFabián Lorenzo-DíazSilvia RussiHansel GómezCris Fernández-LópezRosa Pérez-LuqueModesto OrozcoManuel EspinosaMiquel CollPublished in: Proceedings of the National Academy of Sciences of the United States of America (2017)
Relaxases are metal-dependent nucleases that break and join DNA for the initiation and completion of conjugative bacterial gene transfer. Conjugation is the main process through which antibiotic resistance spreads among bacteria, with multidrug-resistant staphylococci and streptococci infections posing major threats to human health. The MOBV family of relaxases accounts for approximately 85% of all relaxases found in Staphylococcus aureus isolates. Here, we present six structures of the MOBV relaxase MobM from the promiscuous plasmid pMV158 in complex with several origin of transfer DNA fragments. A combined structural, biochemical, and computational approach reveals that MobM follows a previously uncharacterized histidine/metal-dependent DNA processing mechanism, which involves the formation of a covalent phosphoramidate histidine-DNA adduct for cell-to-cell transfer. We discuss how the chemical features of the high-energy phosphorus-nitrogen bond shape the dominant position of MOBV histidine relaxases among small promiscuous plasmids and their preference toward Gram-positive bacteria.
Keyphrases
- circulating tumor
- cell free
- single molecule
- human health
- multidrug resistant
- staphylococcus aureus
- escherichia coli
- risk assessment
- nucleic acid
- single cell
- structural basis
- genome wide
- copy number
- cell therapy
- high resolution
- oxidative stress
- climate change
- crispr cas
- transcription factor
- mass spectrometry
- bone marrow
- genome wide identification
- amino acid