Multidrug-resistant bacteria compensate for the epistasis between resistances
Autor(a) principal: | |
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Data de Publicação: | 2017 |
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/10400.7/748 |
Resumo: | 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. |
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Multidrug-resistant bacteria compensate for the epistasis between resistancesAntibiotic resistanceMicrobial mutationCloningEpistasisMutationAntibioticsStreptomycinBacterial evolutionMutations 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.Fundação para a Ciência e a Tecnologia, European Research Council.Public Library of ScienceARCAMoura de Sousa, JorgeBalbontín, RobertoDurão, PauloGordo, Isabel2017-05-03T14:32:34Z2017-04-182017-04-18T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfapplication/vnd.openxmlformats-officedocument.spreadsheetml.sheetapplication/pdfapplication/vnd.openxmlformats-officedocument.spreadsheetml.sheetapplication/pdfapplication/vnd.openxmlformats-officedocument.spreadsheetml.sheetapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/10400.7/748engMoura 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 74110.1371/journal.pbio.2001741info: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:RCAAP2022-11-29T14:35:08Zoai:arca.igc.gulbenkian.pt:10400.7/748Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:11:58.631768Repositório 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 |
Multidrug-resistant bacteria compensate for the epistasis between resistances |
title |
Multidrug-resistant bacteria compensate for the epistasis between resistances |
spellingShingle |
Multidrug-resistant bacteria compensate for the epistasis between resistances Moura de Sousa, Jorge Antibiotic resistance Microbial mutation Cloning Epistasis Mutation Antibiotics Streptomycin Bacterial evolution |
title_short |
Multidrug-resistant bacteria compensate for the epistasis between resistances |
title_full |
Multidrug-resistant bacteria compensate for the epistasis between resistances |
title_fullStr |
Multidrug-resistant bacteria compensate for the epistasis between resistances |
title_full_unstemmed |
Multidrug-resistant bacteria compensate for the epistasis between resistances |
title_sort |
Multidrug-resistant bacteria compensate for the epistasis between resistances |
author |
Moura de Sousa, Jorge |
author_facet |
Moura de Sousa, Jorge Balbontín, Roberto Durão, Paulo Gordo, Isabel |
author_role |
author |
author2 |
Balbontín, Roberto Durão, Paulo Gordo, Isabel |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
ARCA |
dc.contributor.author.fl_str_mv |
Moura de Sousa, Jorge Balbontín, Roberto Durão, Paulo Gordo, Isabel |
dc.subject.por.fl_str_mv |
Antibiotic resistance Microbial mutation Cloning Epistasis Mutation Antibiotics Streptomycin Bacterial evolution |
topic |
Antibiotic resistance Microbial mutation Cloning Epistasis Mutation Antibiotics Streptomycin Bacterial evolution |
description |
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. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-05-03T14:32:34Z 2017-04-18 2017-04-18T00:00:00Z |
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/10400.7/748 |
url |
http://hdl.handle.net/10400.7/748 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
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 10.1371/journal.pbio.2001741 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/vnd.openxmlformats-officedocument.spreadsheetml.sheet application/pdf application/vnd.openxmlformats-officedocument.spreadsheetml.sheet application/pdf application/vnd.openxmlformats-officedocument.spreadsheetml.sheet application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Public Library of Science |
publisher.none.fl_str_mv |
Public Library of Science |
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 |
reponame_str |
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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