Structural basis of a histidine-DNA nicking/joining mechanism for gene transfer and promiscuous spread of antibiotic resistance
Abstract
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. In conclusion, 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.
- Authors:
-
[1];
- Barcelona Institute of Science and Technology, Barcelona (Spain); Molecular Biology Institute of Barcelona, Barcelona (Spain); International Institute of Molecular and Cell Biology in Warsaw, Warsaw (Poland)
- Barcelona Institute of Science and Technology, Barcelona (Spain); Molecular Biology Institute of Barcelona, Barcelona (Spain); CELLS-ALBA Synchrotron Light Source, Cerdanyola del Valles (Spain)
- Consejo Superior de Investigaciones Cientificas, Madrid (Spain)
- Barcelona Institute of Science and Technology, Barcelona (Spain); Molecular Biology Institute of Barcelona, Barcelona (Spain); SLAC National Accelerator Lab., Menlo Park, CA (United States)
- Barcelona Institute of Science and Technology, Barcelona (Spain); Barcelona Institute of Science and Technology, Barcelona (Spain)
- Barcelona Institute of Science and Technology, Barcelona (Spain); Molecular Biology Institute of Barcelona, Barcelona (Spain)
- Barcelona Institute of Science and Technology, Barcelona (Spain); Barcelona Institute of Science and Technology, Barcelona (Spain); Univ. of Barcelona, Barcelona (Spain)
- Publication Date:
- Research Org.:
- SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1390289
- Grant/Contract Number:
- AC02-76SF00515; SGR2009-1309; 2014-SGR134; 2014-SGR1530; GA No. 260644; ERC_SimDNA; BFU2008-02372/BMC; CSD-2006-23; BFU2011-22588; BIO2013-49148-C2-2-R; BFU2014-53550-P; BIO2015-69085-REDC; BIO2015-64802; CSD-2008/00013
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 114; Journal Issue: 32; Journal ID: ISSN 0027-8424
- Publisher:
- National Academy of Sciences, Washington, DC (United States)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; histidine relaxase; antibiotic resistance; horizontal gene transfer; X-ray structure; Staphylococcus aureus
Citation Formats
Pluta, Radoslaw, Boer, D. Roeland, Lorenzo-Diaz, Fabian, Russi, Silvia, Gomez, Hansel, Fernandez-Lopez, Cris, Perez-Luque, Rosa, Orozco, Modesto, Espinosa, Manuel, and Coll, Miquel. Structural basis of a histidine-DNA nicking/joining mechanism for gene transfer and promiscuous spread of antibiotic resistance. United States: N. p., 2017.
Web. doi:10.1073/pnas.1702971114.
Pluta, Radoslaw, Boer, D. Roeland, Lorenzo-Diaz, Fabian, Russi, Silvia, Gomez, Hansel, Fernandez-Lopez, Cris, Perez-Luque, Rosa, Orozco, Modesto, Espinosa, Manuel, & Coll, Miquel. Structural basis of a histidine-DNA nicking/joining mechanism for gene transfer and promiscuous spread of antibiotic resistance. United States. https://doi.org/10.1073/pnas.1702971114
Pluta, Radoslaw, Boer, D. Roeland, Lorenzo-Diaz, Fabian, Russi, Silvia, Gomez, Hansel, Fernandez-Lopez, Cris, Perez-Luque, Rosa, Orozco, Modesto, Espinosa, Manuel, and Coll, Miquel. Mon .
"Structural basis of a histidine-DNA nicking/joining mechanism for gene transfer and promiscuous spread of antibiotic resistance". United States. https://doi.org/10.1073/pnas.1702971114. https://www.osti.gov/servlets/purl/1390289.
@article{osti_1390289,
title = {Structural basis of a histidine-DNA nicking/joining mechanism for gene transfer and promiscuous spread of antibiotic resistance},
author = {Pluta, Radoslaw and Boer, D. Roeland and Lorenzo-Diaz, Fabian and Russi, Silvia and Gomez, Hansel and Fernandez-Lopez, Cris and Perez-Luque, Rosa and Orozco, Modesto and Espinosa, Manuel and Coll, Miquel},
abstractNote = {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. In conclusion, 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.},
doi = {10.1073/pnas.1702971114},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 32,
volume = 114,
place = {United States},
year = {Mon Jul 24 00:00:00 EDT 2017},
month = {Mon Jul 24 00:00:00 EDT 2017}
}
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