Synthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer

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, synthet...

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Autores principales:	María Getino, David J. Sanabria-Ríos, Raúl Fernández-López, Javier Campos-Gómez, José M. Sánchez-López, Antonio Fernández, Néstor M. Carballeira, Fernando de la Cruz
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b9ca3b153caf48bea5b2697388ee788d
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spelling	oai:doaj.org-article:b9ca3b153caf48bea5b2697388ee788d2021-11-15T15:41:31ZSynthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer10.1128/mBio.01032-152150-7511https://doaj.org/article/b9ca3b153caf48bea5b2697388ee788d2015-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01032-15https://doaj.org/toc/2150-7511ABSTRACT 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.María GetinoDavid J. Sanabria-RíosRaúl Fernández-LópezJavier Campos-GómezJosé M. Sánchez-LópezAntonio FernándezNéstor M. CarballeiraFernando de la CruzAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 5 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 María Getino David J. Sanabria-Ríos Raúl Fernández-López Javier Campos-Gómez José M. Sánchez-López Antonio Fernández Néstor M. Carballeira Fernando de la Cruz Synthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer
description	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.
format	article
author	María Getino David J. Sanabria-Ríos Raúl Fernández-López Javier Campos-Gómez José M. Sánchez-López Antonio Fernández Néstor M. Carballeira Fernando de la Cruz
author_facet	María Getino David J. Sanabria-Ríos Raúl Fernández-López Javier Campos-Gómez José M. Sánchez-López Antonio Fernández Néstor M. Carballeira Fernando de la Cruz
author_sort	María Getino
title	Synthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer
title_short	Synthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer
title_full	Synthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer
title_fullStr	Synthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer
title_full_unstemmed	Synthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer
title_sort	synthetic fatty acids prevent plasmid-mediated horizontal gene transfer
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/b9ca3b153caf48bea5b2697388ee788d
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Synthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer

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