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Positive Epistasis Drives the Acquisition of Multidrug Resistance

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Resumo:The evolution of multiple antibiotic resistance is an increasing global problem. Resistance mutations are known to impair fitness, and the evolution of resistance to multiple drugs depends both on their costs individually and on how they interact-epistasis. Information on the level of epistasis between antibiotic resistance mutations is of key importance to understanding epistasis amongst deleterious alleles, a key theoretical question, and to improving public health measures. Here we show that in an antibiotic-free environment the cost of multiple resistance is smaller than expected, a signature of pervasive positive epistasis among alleles that confer resistance to antibiotics. Competition assays reveal that the cost of resistance to a given antibiotic is dependent on the presence of resistance alleles for other antibiotics.
Autores principais:Trindade, S.
Outros Autores:Sousa, A.; Xavier, KB.; Dionisio, F.; Ferreira, MG.; Gordo, I.
Assunto:ANTIBIOTIC-RESISTANCE ESCHERICHIA-COLI MYCOBACTERIUM-TUBERCULOSIS DELETERIOUS MUTATIONS COMPENSATORY MUTATIONS FITNESS COSTS
Ano:2009
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Repositório do GIMM – Gulbenkian Institute for Molecular Medicine
Idioma:inglês
Origem:ARCA
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author Trindade, S.
author2 Sousa, A.
Xavier, KB.
Dionisio, F.
Ferreira, MG.
Gordo, I.
author2_role author
author
author
author
author
author_facet Trindade, S.
Sousa, A.
Xavier, KB.
Dionisio, F.
Ferreira, MG.
Gordo, I.
author_role author
contributor_name_str_mv ARCA
country_str PT
creators_json_txt [{\"Person.name\":\"Trindade, S.\"},{\"Person.name\":\"Sousa, A.\"},{\"Person.name\":\"Xavier, KB.\"},{\"Person.name\":\"Dionisio, F.\"},{\"Person.name\":\"Ferreira, MG.\"},{\"Person.name\":\"Gordo, I.\"}]
datacite.contributors.contributor.contributorName.fl_str_mv ARCA
datacite.creators.creator.creatorName.fl_str_mv Trindade, S.
Sousa, A.
Xavier, KB.
Dionisio, F.
Ferreira, MG.
Gordo, I.
datacite.date.Accepted.fl_str_mv 2009-07-01T00:00:00Z
datacite.date.available.fl_str_mv 2010-08-11T13:30:16Z
datacite.date.embargoed.fl_str_mv 2010-08-11T13:30:16Z
datacite.rights.fl_str_mv http://purl.org/coar/access_right/c_abf2
datacite.subjects.subject.fl_str_mv ANTIBIOTIC-RESISTANCE
ESCHERICHIA-COLI
MYCOBACTERIUM-TUBERCULOSIS
DELETERIOUS MUTATIONS
COMPENSATORY MUTATIONS
FITNESS COSTS
datacite.titles.title.fl_str_mv Positive Epistasis Drives the Acquisition of Multidrug Resistance
dc.contributor.none.fl_str_mv ARCA
dc.creator.none.fl_str_mv Trindade, S.
Sousa, A.
Xavier, KB.
Dionisio, F.
Ferreira, MG.
Gordo, I.
dc.date.Accepted.fl_str_mv 2009-07-01T00:00:00Z
dc.date.available.fl_str_mv 2010-08-11T13:30:16Z
dc.date.embargoed.fl_str_mv 2010-08-11T13:30:16Z
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv http://hdl.handle.net/10400.7/165
dc.language.none.fl_str_mv eng
dc.publisher.none.fl_str_mv PLOS
dc.rights.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.subject.none.fl_str_mv ANTIBIOTIC-RESISTANCE
ESCHERICHIA-COLI
MYCOBACTERIUM-TUBERCULOSIS
DELETERIOUS MUTATIONS
COMPENSATORY MUTATIONS
FITNESS COSTS
dc.title.fl_str_mv Positive Epistasis Drives the Acquisition of Multidrug Resistance
dc.type.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
description The evolution of multiple antibiotic resistance is an increasing global problem. Resistance mutations are known to impair fitness, and the evolution of resistance to multiple drugs depends both on their costs individually and on how they interact-epistasis. Information on the level of epistasis between antibiotic resistance mutations is of key importance to understanding epistasis amongst deleterious alleles, a key theoretical question, and to improving public health measures. Here we show that in an antibiotic-free environment the cost of multiple resistance is smaller than expected, a signature of pervasive positive epistasis among alleles that confer resistance to antibiotics. Competition assays reveal that the cost of resistance to a given antibiotic is dependent on the presence of resistance alleles for other antibiotics.
dirty 0
eu_rights_str_mv openAccess
format article
fulltext.url.fl_str_mv https://arca.gimm.pt/bitstreams/4e1f100e-731b-4d6f-aa76-542ba3f754de/download
id arca_7eac44c4feaf2c040ae792f167642942
identifier.url.fl_str_mv http://hdl.handle.net/10400.7/165
instacron_str arca
institution Repositório do GIMM – Gulbenkian Institute for Molecular Medicine
instname_str Repositório do GIMM – Gulbenkian Institute for Molecular Medicine
language eng
network_acronym_str arca
network_name_str ARCA
oai_identifier_str oai:arca.gimm.pt:10400.7/165
organization_str_mv urn:organizationAcronym:arca
person_str_mv Trindade, S.
Sousa, A.
Xavier, KB.
Dionisio, F.
Ferreira, MG.
Gordo, I.
publishDate 2009
publisher.none.fl_str_mv PLOS
reponame_str ARCA
repository_id_str urn:repositoryAcronym:arca
service_str_mv urn:repositoryAcronym:arca
spelling engPLOSptThe evolution of multiple antibiotic resistance is an increasing global problem. Resistance mutations are known to impair fitness, and the evolution of resistance to multiple drugs depends both on their costs individually and on how they interact-epistasis. Information on the level of epistasis between antibiotic resistance mutations is of key importance to understanding epistasis amongst deleterious alleles, a key theoretical question, and to improving public health measures. Here we show that in an antibiotic-free environment the cost of multiple resistance is smaller than expected, a signature of pervasive positive epistasis among alleles that confer resistance to antibiotics. Competition assays reveal that the cost of resistance to a given antibiotic is dependent on the presence of resistance alleles for other antibiotics.application/pdfptPositive Epistasis Drives the Acquisition of Multidrug ResistanceTrindade, S.Sousa, A.Xavier, KB.Dionisio, F.Ferreira, MG.Gordo, I.HostingInstitutionOrganizationalARCAe-mailmailto:arca.repository@gimm.ptarca.repository@gimm.ptISSNIsPartOf1553-73902010-08-11T13:30:16Z2009-072009-07-01T00:00:00ZHandlehttp://hdl.handle.net/10400.7/165http://purl.org/coar/access_right/c_abf2open accessANTIBIOTIC-RESISTANCEESCHERICHIA-COLIMYCOBACTERIUM-TUBERCULOSISDELETERIOUS MUTATIONSCOMPENSATORY MUTATIONSFITNESS COSTS336169 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://arca.gimm.pt/bitstreams/4e1f100e-731b-4d6f-aa76-542ba3f754de/downloadPLOS Genetics19
spellingShingle Positive Epistasis Drives the Acquisition of Multidrug Resistance
Trindade, S.
ANTIBIOTIC-RESISTANCE
ESCHERICHIA-COLI
MYCOBACTERIUM-TUBERCULOSIS
DELETERIOUS MUTATIONS
COMPENSATORY MUTATIONS
FITNESS COSTS
status SINGLETON
subject.fl_str_mv ANTIBIOTIC-RESISTANCE
ESCHERICHIA-COLI
MYCOBACTERIUM-TUBERCULOSIS
DELETERIOUS MUTATIONS
COMPENSATORY MUTATIONS
FITNESS COSTS
title Positive Epistasis Drives the Acquisition of Multidrug Resistance
title_full Positive Epistasis Drives the Acquisition of Multidrug Resistance
title_fullStr Positive Epistasis Drives the Acquisition of Multidrug Resistance
title_full_unstemmed Positive Epistasis Drives the Acquisition of Multidrug Resistance
title_short Positive Epistasis Drives the Acquisition of Multidrug Resistance
title_sort Positive Epistasis Drives the Acquisition of Multidrug Resistance
topic ANTIBIOTIC-RESISTANCE
ESCHERICHIA-COLI
MYCOBACTERIUM-TUBERCULOSIS
DELETERIOUS MUTATIONS
COMPENSATORY MUTATIONS
FITNESS COSTS
topic_facet ANTIBIOTIC-RESISTANCE
ESCHERICHIA-COLI
MYCOBACTERIUM-TUBERCULOSIS
DELETERIOUS MUTATIONS
COMPENSATORY MUTATIONS
FITNESS COSTS
url http://hdl.handle.net/10400.7/165
visible 1