dc.contributor.author	Moura de Sousa, Jorge
dc.contributor.author	Balbontín, Roberto
dc.contributor.author	Durão, Paulo
dc.contributor.author	Gordo, Isabel
dc.date.accessioned	2017-05-03T14:32:34Z
dc.date.available	2017-05-03T14:32:34Z
dc.date.issued	2017-04-18
dc.description.abstract	Mutations conferring resistance to antibiotics are typically costly in the absence of the drug, but bacteria can reduce this cost by acquiring compensatory mutations. Thus, the rate of acquisition of compensatory mutations and their effects are key for the maintenance and dissemination of antibiotic resistances. While compensation for single resistances has been extensively studied, compensatory evolution of multiresistant bacteria remains unexplored. Importantly, since resistance mutations often interact epistatically, compensation of multiresistant bacteria may significantly differ from that of single-resistant strains. We used experimental evolution, next-generation sequencing, in silico simulations, and genome editing to compare the compensatory process of a streptomycin and rifampicin double-resistant Escherichia coli with those of single-resistant clones. We demonstrate that low-fitness double-resistant bacteria compensate faster than single-resistant strains due to the acquisition of compensatory mutations with larger effects. Strikingly, we identified mutations that only compensate for double resistance, being neutral or deleterious in sensitive or single-resistant backgrounds. Moreover, we show that their beneficial effects strongly decrease or disappear in conditions where the epistatic interaction between resistance alleles is absent, demonstrating that these mutations compensate for the epistasis. In summary, our data indicate that epistatic interactions between antibiotic resistances, leading to large fitness costs, possibly open alternative paths for rapid compensatory evolution, thereby potentially stabilizing costly multiple resistances in bacterial populations.	pt_PT
dc.description.sponsorship	Fundação para a Ciência e a Tecnologia, European Research Council.	pt_PT
dc.description.version	info:eu-repo/semantics/publishedVersion	pt_PT
dc.identifier.citation	Moura de Sousa J, Balbontı ́ n R, Dur ã o P, Gordo I (2017) Multidru g-resistant bacteria compensate for the epistasis between resistance s. PLoS Biol 15(4): e2001741. https://do i.org/ 10.1371/ journal.pbio.2001 741	pt_PT
dc.identifier.doi	10.1371/journal.pbio.2001741	pt_PT
dc.identifier.uri	http://hdl.handle.net/10400.7/748
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	Public Library of Science	pt_PT
dc.relation	SFRH/BPD/109517/ 2015	pt_PT
dc.relation	EXPLORING ADAPTATION BEYOND FITNESS PEAKS
dc.relation.publisherversion	http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2001741	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	pt_PT
dc.subject	Antibiotic resistance	pt_PT
dc.subject	Microbial mutation	pt_PT
dc.subject	Cloning	pt_PT
dc.subject	Epistasis	pt_PT
dc.subject	Mutation	pt_PT
dc.subject	Antibiotics	pt_PT
dc.subject	Streptomycin	pt_PT
dc.subject	Bacterial evolution	pt_PT
dc.title	Multidrug-resistant bacteria compensate for the epistasis between resistances	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.awardTitle	EXPLORING ADAPTATION BEYOND FITNESS PEAKS
oaire.awardURI	info:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F89151%2F2012/PT
oaire.citation.endPage	24	pt_PT
oaire.citation.issue	4	pt_PT
oaire.citation.startPage	1	pt_PT
oaire.citation.title	PLoS Biology	pt_PT
oaire.citation.volume	15	pt_PT
project.funder.identifier	http://doi.org/10.13039/501100001871
project.funder.name	Fundação para a Ciência e a Tecnologia
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT
relation.isProjectOfPublication	85cd72e1-1c33-480c-ae77-f1effb2ee9cc
relation.isProjectOfPublication.latestForDiscovery	85cd72e1-1c33-480c-ae77-f1effb2ee9cc

Multidrug-resistant bacteria compensate for the epistasis between resistances

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