title: Type IV traffic ATPase TrwD as molecular target to inhibit bacterial conjugation.
abstract: Bacterial conjugation is the main mechanism responsible for the dissemination of antibiotic resistance genes. Hence, the search for specific conjugation inhibitors is paramount in the fight against the spread of these genes. In this pursuit, unsaturated fatty acids have been found to specifically inhibit bacterial conjugation. Despite the growing interest on these compounds, their mode of action and their specific target remain unknown. Here, we identified TrwD, a Type IV secretion traffic ATPase, as the molecular target for fatty acid-mediated inhibition of conjugation. Moreover, 2-alkynoic fatty acids, which are also potent inhibitors of bacterial conjugation, are also powerful inhibitors of the ATPase activity of TrwD. Characterization of the kinetic parameters of ATPase inhibition has led us to identify the catalytic mechanism by which fatty acids exert their activity. These results open a new avenue for the rational design of inhibitors of bacterial conjugation in the fight against the dissemination of antibiotic resistance genes.
authors.affiliation: Departamento de Biología Molecular and Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Universidad de Cantabria-CSIC, Santander, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Ripoll-Rozada
authors.affiliation: Departamento de Biología Molecular and Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Universidad de Cantabria-CSIC, Santander, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: García-Cazorla
authors.affiliation: Departamento de Biología Molecular and Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Universidad de Cantabria-CSIC, Santander, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Getino
authors.affiliation: Departamento de Biología Molecular and Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Universidad de Cantabria-CSIC, Santander, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Machón
authors.affiliation: Inter American University of Puerto Rico-Metropolitan Campus, Faculty of Science and Technology, San Juan, Puerto Rico.
authors.forename: David
authors.initials: D
authors.lastname: Sanabria-Ríos
authors.affiliation: Departamento de Biología Molecular and Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Universidad de Cantabria-CSIC, Santander, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: de la Cruz
authors.affiliation: Departamento de Biología Molecular and Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Universidad de Cantabria-CSIC, Santander, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Cabezón
authors.affiliation: Departamento de Biología Molecular and Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Universidad de Cantabria-CSIC, Santander, Spain.
authors.forename: Ignacio
authors.identifier: 0000-0002-1342-9370
authors.initials: I
authors.lastname: Arechaga
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics; D058947:Bacterial Secretion Systems / Q000737:chemistry; D003227:Conjugation, Genetic / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis / Q000494:pharmacology*; D007700:Kinetics; D019787:Linoleic Acid / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D010957:Plasmids
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D029968:Escherichia coli Proteins; D005231:Fatty Acids, Unsaturated; D019787:Linoleic Acid; D000251:Adenosine Triphosphatases; C108667:TrwD protein, E coli