Positive epistasis drives the acquisition of multidrug resistance
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.7/32 |
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. Surprisingly we find that a significant fraction of resistant mutations can be beneficial in certain resistant genetic backgrounds, that some double resistances entail no measurable cost, and that some allelic combinations are hotspots for rapid compensation. These results provide additional insight as to why multi-resistant bacteria are so prevalent and reveal an extra layer of complexity on epistatic patterns previously unrecognized, since it is hidden in genome-wide studies of genetic interactions using gene knockouts |
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Positive epistasis drives the acquisition of multidrug resistanceEpistasis, GeneticEvolution, MolecularDrug Resistance, Multiple, BacterialThe 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. Surprisingly we find that a significant fraction of resistant mutations can be beneficial in certain resistant genetic backgrounds, that some double resistances entail no measurable cost, and that some allelic combinations are hotspots for rapid compensation. These results provide additional insight as to why multi-resistant bacteria are so prevalent and reveal an extra layer of complexity on epistatic patterns previously unrecognized, since it is hidden in genome-wide studies of genetic interactions using gene knockoutsARCATrindade, S.Sousa, A.Xavier, K.B.Dionísio, F.Ferreira, M.G.Gordo, I.2009-09-29T16:56:44Z2009-072009-07-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.7/32engTrindade S, Sousa A, Xavier KB, Dionisio F, Ferreira MG, Gordo I. (2009). "Positive epistasis drives the acquisition of multidrug resistance".Plos Genetics. 5(7): e10005781553-7404https://doi.org/10.1371/journal.pgen.1000578info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-11-29T14:34:34Zoai:arca.igc.gulbenkian.pt:10400.7/32Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:11:32.177966Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Positive epistasis drives the acquisition of multidrug resistance |
title |
Positive epistasis drives the acquisition of multidrug resistance |
spellingShingle |
Positive epistasis drives the acquisition of multidrug resistance Trindade, S. Epistasis, Genetic Evolution, Molecular Drug Resistance, Multiple, Bacterial |
title_short |
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_sort |
Positive epistasis drives the acquisition of multidrug resistance |
author |
Trindade, S. |
author_facet |
Trindade, S. Sousa, A. Xavier, K.B. Dionísio, F. Ferreira, M.G. Gordo, I. |
author_role |
author |
author2 |
Sousa, A. Xavier, K.B. Dionísio, F. Ferreira, M.G. Gordo, I. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
ARCA |
dc.contributor.author.fl_str_mv |
Trindade, S. Sousa, A. Xavier, K.B. Dionísio, F. Ferreira, M.G. Gordo, I. |
dc.subject.por.fl_str_mv |
Epistasis, Genetic Evolution, Molecular Drug Resistance, Multiple, Bacterial |
topic |
Epistasis, Genetic Evolution, Molecular Drug Resistance, Multiple, Bacterial |
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. Surprisingly we find that a significant fraction of resistant mutations can be beneficial in certain resistant genetic backgrounds, that some double resistances entail no measurable cost, and that some allelic combinations are hotspots for rapid compensation. These results provide additional insight as to why multi-resistant bacteria are so prevalent and reveal an extra layer of complexity on epistatic patterns previously unrecognized, since it is hidden in genome-wide studies of genetic interactions using gene knockouts |
publishDate |
2009 |
dc.date.none.fl_str_mv |
2009-09-29T16:56:44Z 2009-07 2009-07-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.7/32 |
url |
http://hdl.handle.net/10400.7/32 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Trindade S, Sousa A, Xavier KB, Dionisio F, Ferreira MG, Gordo I. (2009). "Positive epistasis drives the acquisition of multidrug resistance".Plos Genetics. 5(7): e1000578 1553-7404 https://doi.org/10.1371/journal.pgen.1000578 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799130571370135552 |