Conjugation Inhibitors Effectively Prevent Plasmid Transmission in Natural Environments

ABSTRACT Plasmid conjugation is a major route for the spread of antibiotic resistance genes. Inhibiting conjugation has been proposed as a feasible strategy to stop or delay the propagation of antibiotic resistance genes. Several compounds have been shown to be conjugation inhibitors in vitro, speci...

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Autores principales:	Carolina Palencia-Gándara, María Getino, Gabriel Moyano, Santiago Redondo, Raúl Fernández-López, Bruno González-Zorn, Fernando de la Cruz
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	Escherichia coli bacterial conjugation antibiotic resistance conjugation inhibitor microcosm gut Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5d3c0919f1ca46d5a1ed5d263e32718d
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spelling	oai:doaj.org-article:5d3c0919f1ca46d5a1ed5d263e32718d2021-11-10T18:37:52ZConjugation Inhibitors Effectively Prevent Plasmid Transmission in Natural Environments10.1128/mBio.01277-212150-7511https://doaj.org/article/5d3c0919f1ca46d5a1ed5d263e32718d2021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01277-21https://doaj.org/toc/2150-7511ABSTRACT Plasmid conjugation is a major route for the spread of antibiotic resistance genes. Inhibiting conjugation has been proposed as a feasible strategy to stop or delay the propagation of antibiotic resistance genes. Several compounds have been shown to be conjugation inhibitors in vitro, specifically targeting the plasmid horizontal transfer machinery. However, the in vivo efficiency and the applicability of these compounds to clinical and environmental settings remained untested. Here we show that the synthetic fatty acid 2-hexadecynoic acid (2-HDA), when used as a fish food supplement, lowers the conjugation frequency of model plasmids up to 10-fold in controlled water microcosms. When added to the food for mice, 2-HDA diminished the conjugation efficiency 50-fold in controlled plasmid transfer assays carried out in the mouse gut. These results demonstrate the in vivo efficiency of conjugation inhibitors, paving the way for their potential application in clinical and environmental settings. IMPORTANCE The spread of antibiotic resistance is considered one of the major threats for global health in the immediate future. A key reason for the speed at which antibiotic resistance spread is the ability of bacteria to share genes with each other. Antibiotic resistance genes harbored in plasmids can be easily transferred to commensal and pathogenic bacteria through a process known as bacterial conjugation. Blocking conjugation is thus a potentially useful strategy to curtail the propagation of antibiotic resistance. Conjugation inhibitors (COINS) are a series of compounds that block conjugation in vitro. Here we show that COINS efficiently block plasmid transmission in two controlled natural environments, water microcosms and the mouse gut. These observations indicate that COIN therapy can be used to prevent the spread of antibiotic resistance.Carolina Palencia-GándaraMaría GetinoGabriel MoyanoSantiago RedondoRaúl Fernández-LópezBruno González-ZornFernando de la CruzAmerican Society for MicrobiologyarticleEscherichia colibacterial conjugationantibiotic resistanceconjugation inhibitormicrocosmgutMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Escherichia coli bacterial conjugation antibiotic resistance conjugation inhibitor microcosm gut Microbiology QR1-502
spellingShingle	Escherichia coli bacterial conjugation antibiotic resistance conjugation inhibitor microcosm gut Microbiology QR1-502 Carolina Palencia-Gándara María Getino Gabriel Moyano Santiago Redondo Raúl Fernández-López Bruno González-Zorn Fernando de la Cruz Conjugation Inhibitors Effectively Prevent Plasmid Transmission in Natural Environments
description	ABSTRACT Plasmid conjugation is a major route for the spread of antibiotic resistance genes. Inhibiting conjugation has been proposed as a feasible strategy to stop or delay the propagation of antibiotic resistance genes. Several compounds have been shown to be conjugation inhibitors in vitro, specifically targeting the plasmid horizontal transfer machinery. However, the in vivo efficiency and the applicability of these compounds to clinical and environmental settings remained untested. Here we show that the synthetic fatty acid 2-hexadecynoic acid (2-HDA), when used as a fish food supplement, lowers the conjugation frequency of model plasmids up to 10-fold in controlled water microcosms. When added to the food for mice, 2-HDA diminished the conjugation efficiency 50-fold in controlled plasmid transfer assays carried out in the mouse gut. These results demonstrate the in vivo efficiency of conjugation inhibitors, paving the way for their potential application in clinical and environmental settings. IMPORTANCE The spread of antibiotic resistance is considered one of the major threats for global health in the immediate future. A key reason for the speed at which antibiotic resistance spread is the ability of bacteria to share genes with each other. Antibiotic resistance genes harbored in plasmids can be easily transferred to commensal and pathogenic bacteria through a process known as bacterial conjugation. Blocking conjugation is thus a potentially useful strategy to curtail the propagation of antibiotic resistance. Conjugation inhibitors (COINS) are a series of compounds that block conjugation in vitro. Here we show that COINS efficiently block plasmid transmission in two controlled natural environments, water microcosms and the mouse gut. These observations indicate that COIN therapy can be used to prevent the spread of antibiotic resistance.
format	article
author	Carolina Palencia-Gándara María Getino Gabriel Moyano Santiago Redondo Raúl Fernández-López Bruno González-Zorn Fernando de la Cruz
author_facet	Carolina Palencia-Gándara María Getino Gabriel Moyano Santiago Redondo Raúl Fernández-López Bruno González-Zorn Fernando de la Cruz
author_sort	Carolina Palencia-Gándara
title	Conjugation Inhibitors Effectively Prevent Plasmid Transmission in Natural Environments
title_short	Conjugation Inhibitors Effectively Prevent Plasmid Transmission in Natural Environments
title_full	Conjugation Inhibitors Effectively Prevent Plasmid Transmission in Natural Environments
title_fullStr	Conjugation Inhibitors Effectively Prevent Plasmid Transmission in Natural Environments
title_full_unstemmed	Conjugation Inhibitors Effectively Prevent Plasmid Transmission in Natural Environments
title_sort	conjugation inhibitors effectively prevent plasmid transmission in natural environments
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/5d3c0919f1ca46d5a1ed5d263e32718d
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Conjugation Inhibitors Effectively Prevent Plasmid Transmission in Natural Environments

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