Enhanced Survival of Rifampin- and Streptomycin-Resistant Escherichia coli Inside Macrophages

Detalhes bibliográficos
Autor(a) principal: Durão, Paulo
Data de Publicação: 2016
Outros Autores: Gülereşi, Daniela, Proença, João, Gordo, Isabel
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.7/871
Resumo: The deposited article is a post-print version and has been submitted to peer review.
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spelling Enhanced Survival of Rifampin- and Streptomycin-Resistant Escherichia coli Inside MacrophagesAnimalsAnti-Bacterial AgentsDrug Resistance, BacterialDrug Resistance, Multiple, BacterialEscherichia coliMacrophagesMiceRAW 264.7 CellsReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionRifampinStreptomycinThe deposited article is a post-print version and has been submitted to peer review.This deposit is composed by the main article plus the supplementary materials of the publication.The evolution of multiple-antibiotic-resistant bacteria is an increasing global problem. Even though mutations causing resistance usually incur a fitness cost in the absence of antibiotics, the magnitude of such costs varies across environments and genomic backgrounds. We studied how the combination of mutations that confer resistance to rifampin (Rif(r)) and streptomycin (Str(r)) affects the fitness of Escherichia coli when it interacts with cells from the immune system, i.e., macrophages (Mϕs). We found that 13 Rif(r) Str(r) doubly resistant genotypes, of the 16 tested, show a survival advantage inside Mϕs, indicating that double resistance can be highly beneficial in this environment. Our results suggest that there are multiple paths to acquire multiple-drug resistance in this context, i.e., if a clone carrying Rif(r) allele H526 or S531 acquires a second mutation conferring Str(r), the resulting double mutant has a high probability of showing increased survival inside Mϕs. On the other hand, we found two cases of sign epistasis between mutations, leading to a significant decrease in bacterial survival. Remarkably, infection of Mϕs with one of these combinations, K88R+H526Y, resulted in an altered pattern of gene expression in the infected Mϕs. This indicates that the fitness effects of resistance may depend on the pattern of gene expression of infected host cells. Notwithstanding the benefits of resistance found inside Mϕs, the Rif(r) Str(r) mutants have massive fitness costs when the bacteria divide outside Mϕs, indicating that the maintenance of double resistance may depend on the time spent within and outside phagocytic cells.This study received funding from the European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement 260421-ECOADAPT. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.ARCADurão, PauloGülereşi, DanielaProença, JoãoGordo, Isabel2018-05-18T12:00:05Z2016-092016-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/10400.7/871engDurão P, Güleres¸i D, Proença J, Gordo I. 2016. Enhanced survival of rifampin- and streptomycin-resistant Escherichia coli inside macrophages. Antimicrob Agents Chemother 60:4324 –4332. doi:10.1128/AAC.00624-16.10.1128/AAC.00624-16info: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:RCAAP2022-11-29T14:35:17Zoai:arca.igc.gulbenkian.pt:10400.7/871Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:12:05.033498Repositório 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 Enhanced Survival of Rifampin- and Streptomycin-Resistant Escherichia coli Inside Macrophages
title Enhanced Survival of Rifampin- and Streptomycin-Resistant Escherichia coli Inside Macrophages
spellingShingle Enhanced Survival of Rifampin- and Streptomycin-Resistant Escherichia coli Inside Macrophages
Durão, Paulo
Animals
Anti-Bacterial Agents
Drug Resistance, Bacterial
Drug Resistance, Multiple, Bacterial
Escherichia coli
Macrophages
Mice
RAW 264.7 Cells
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Rifampin
Streptomycin
title_short Enhanced Survival of Rifampin- and Streptomycin-Resistant Escherichia coli Inside Macrophages
title_full Enhanced Survival of Rifampin- and Streptomycin-Resistant Escherichia coli Inside Macrophages
title_fullStr Enhanced Survival of Rifampin- and Streptomycin-Resistant Escherichia coli Inside Macrophages
title_full_unstemmed Enhanced Survival of Rifampin- and Streptomycin-Resistant Escherichia coli Inside Macrophages
title_sort Enhanced Survival of Rifampin- and Streptomycin-Resistant Escherichia coli Inside Macrophages
author Durão, Paulo
author_facet Durão, Paulo
Gülereşi, Daniela
Proença, João
Gordo, Isabel
author_role author
author2 Gülereşi, Daniela
Proença, João
Gordo, Isabel
author2_role author
author
author
dc.contributor.none.fl_str_mv ARCA
dc.contributor.author.fl_str_mv Durão, Paulo
Gülereşi, Daniela
Proença, João
Gordo, Isabel
dc.subject.por.fl_str_mv Animals
Anti-Bacterial Agents
Drug Resistance, Bacterial
Drug Resistance, Multiple, Bacterial
Escherichia coli
Macrophages
Mice
RAW 264.7 Cells
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Rifampin
Streptomycin
topic Animals
Anti-Bacterial Agents
Drug Resistance, Bacterial
Drug Resistance, Multiple, Bacterial
Escherichia coli
Macrophages
Mice
RAW 264.7 Cells
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Rifampin
Streptomycin
description The deposited article is a post-print version and has been submitted to peer review.
publishDate 2016
dc.date.none.fl_str_mv 2016-09
2016-09-01T00:00:00Z
2018-05-18T12:00:05Z
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/10400.7/871
url http://hdl.handle.net/10400.7/871
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Durão P, Güleres¸i D, Proença J, Gordo I. 2016. Enhanced survival of rifampin- and streptomycin-resistant Escherichia coli inside macrophages. Antimicrob Agents Chemother 60:4324 –4332. doi:10.1128/AAC.00624-16.
10.1128/AAC.00624-16
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
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
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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