@article{10902/7284,
year = {2015},
month = {9},
url = {http://hdl.handle.net/10902/7284},
abstract = {Bacterial conjugation constitutes a major horizontal gene transfer mechanism for the dissemination of antibiotic resistance genes among human pathogens. Antibiotic resistance spread could be halted or diminished by molecules that interfere with the conjugation process. In this work, synthetic 2-alkynoic fatty acids were identified as a novel class of conjugation inhibitors. Their chemical properties were investigated by using the prototype 2-hexadecynoic acid and its derivatives. Essential features of effective inhibitors were the carboxylic group, an optimal long aliphatic chain of 16 carbon atoms, and one unsaturation. Chemical modification of these groups led to inactive or less-active derivatives. Conjugation inhibitors were found to act on the donor cell, affecting a wide number of pathogenic bacterial hosts, including Escherichia, Salmonella, Pseudomonas, and Acinetobacter spp. Conjugation inhibitors were active in inhibiting transfer of IncF, IncW, and IncH plasmids, moderately active against IncI, IncL/M, and IncX plasmids, and inactive against IncP and IncN plasmids. Importantly, the use of 2-hexadecynoic acid avoided the spread of a derepressed IncF plasmid into a recipient population, demonstrating the feasibility of abolishing the dissemination of antimicrobial resistances by blocking bacterial conjugation. IMPORTANCE: Diseases caused by multidrug-resistant bacteria are taking an important toll with respect to human morbidity and mortality. The most relevant antibiotic resistance genes come to human pathogens carried by plasmids, mainly using conjugation as a transmission mechanism. Here, we identified and characterized a series of compounds that were active against several plasmid groups of clinical relevance, in a wide variety of bacterial hosts. These inhibitors might be used for fighting antibiotic-resistance dissemination by inhibiting conjugation. Potential inhibitors could be used in specific settings (e.g., farm, fish factory, or even clinical settings) to investigate their effect in the eradication of undesired resistances.},
organization = {The work performed by the F.D.L.C. group was supported by grants BFU2011-26608 from the Spanish Ministry of Economy and Competitiveness and 612146/FP7-ICT-2013-10 and 282004/FP7-HEALTH-2011-2.3.1-2 from the European Seventh Framework Programme. The work performed by M.G. was supported by a Ph.D. fellowship from the University of Cantabria. The work performed by D.J.S.-R. was supported by the National Center for Research Resources and the National Institute of General Medical Sciences of the National Institutes of Health through grant no. 5P20GM103475-13 and the Interamerican University of Puerto Rico. The work performed by J.C.-G. was supported by an EMBO postdoctoral fellowship, ASTF 402-2010. The work performed by Biomar Microbial Technologies was supported by grant 282004/FP7-HEALTH-2011-2.3.1-2 from the European Seventh Framework Programme.},
publisher = {American Society for Microbiology},
publisher = {MBio. 2015, 6(5), e01032-15},
title = {Synthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer},
author = {Getino Redondo, María and Sanabria Ríos, David J. and Fernández López, Raúl and Campos Gómez, Javier and Sánchez López, José M. and Fernández Medarde, Antonio and Carballeira Cabranes, Néstor M. and Cruz Calahorra, Fernando de la},
}