Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages
Autor(a) principal: | |
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Data de Publicação: | 2013 |
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/10400.7/463 |
Resumo: | Mutations causing antibiotic resistance usually incur a fitness cost in the absence of antibiotics. The magnitude of such costs is known to vary with the environment. Little is known about the fitness effects of antibiotic resistance mutations when bacteria confront the host's immune system. Here, we study the fitness effects of mutations in the rpoB, rpsL, and gyrA genes, which confer resistance to rifampin, streptomycin, and nalidixic acid, respectively. These antibiotics are frequently used in the treatment of bacterial infections. We measured two important fitness traits-growth rate and survival ability-of 12 Escherichia coli K-12 strains, each carrying a single resistance mutation, in the presence of macrophages. Strikingly, we found that 67% of the mutants survived better than the susceptible bacteria in the intracellular niche of the phagocytic cells. In particular, all E. coli streptomycin-resistant mutants exhibited an intracellular advantage. On the other hand, 42% of the mutants incurred a high fitness cost when the bacteria were allowed to divide outside of macrophages. This study shows that single nonsynonymous changes affecting fundamental processes in the cell can contribute to prolonged survival of E. coli in the context of an infection. |
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Increased Survival of Antibiotic-Resistant Escherichia coli inside MacrophagesAnti-Bacterial AgentsEscherichia coli K12Escherichia coli ProteinsMacrophagesMutations causing antibiotic resistance usually incur a fitness cost in the absence of antibiotics. The magnitude of such costs is known to vary with the environment. Little is known about the fitness effects of antibiotic resistance mutations when bacteria confront the host's immune system. Here, we study the fitness effects of mutations in the rpoB, rpsL, and gyrA genes, which confer resistance to rifampin, streptomycin, and nalidixic acid, respectively. These antibiotics are frequently used in the treatment of bacterial infections. We measured two important fitness traits-growth rate and survival ability-of 12 Escherichia coli K-12 strains, each carrying a single resistance mutation, in the presence of macrophages. Strikingly, we found that 67% of the mutants survived better than the susceptible bacteria in the intracellular niche of the phagocytic cells. In particular, all E. coli streptomycin-resistant mutants exhibited an intracellular advantage. On the other hand, 42% of the mutants incurred a high fitness cost when the bacteria were allowed to divide outside of macrophages. This study shows that single nonsynonymous changes affecting fundamental processes in the cell can contribute to prolonged survival of E. coli in the context of an infection.European Research Council, LAO/ITQB, FCT.American Society for MicrobiologyARCAMiskinyte, M.Gordo, I.2015-11-03T12:56:30Z2013-012013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.7/463engIncreased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages Migla Miskinyte and Isabel Gordo Antimicrob. Agents Chemother. January 2013 57:1 189-195; Accepted manuscript posted online 22 October 2012, doi:10.1128/AAC.01632-1210.1128/AAC.01632-12info: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:RCAAP2022-11-29T14:34:51Zoai:arca.igc.gulbenkian.pt:10400.7/463Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:11:44.558031Repositório 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 |
Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages |
title |
Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages |
spellingShingle |
Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages Miskinyte, M. Anti-Bacterial Agents Escherichia coli K12 Escherichia coli Proteins Macrophages |
title_short |
Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages |
title_full |
Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages |
title_fullStr |
Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages |
title_full_unstemmed |
Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages |
title_sort |
Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages |
author |
Miskinyte, M. |
author_facet |
Miskinyte, M. Gordo, I. |
author_role |
author |
author2 |
Gordo, I. |
author2_role |
author |
dc.contributor.none.fl_str_mv |
ARCA |
dc.contributor.author.fl_str_mv |
Miskinyte, M. Gordo, I. |
dc.subject.por.fl_str_mv |
Anti-Bacterial Agents Escherichia coli K12 Escherichia coli Proteins Macrophages |
topic |
Anti-Bacterial Agents Escherichia coli K12 Escherichia coli Proteins Macrophages |
description |
Mutations causing antibiotic resistance usually incur a fitness cost in the absence of antibiotics. The magnitude of such costs is known to vary with the environment. Little is known about the fitness effects of antibiotic resistance mutations when bacteria confront the host's immune system. Here, we study the fitness effects of mutations in the rpoB, rpsL, and gyrA genes, which confer resistance to rifampin, streptomycin, and nalidixic acid, respectively. These antibiotics are frequently used in the treatment of bacterial infections. We measured two important fitness traits-growth rate and survival ability-of 12 Escherichia coli K-12 strains, each carrying a single resistance mutation, in the presence of macrophages. Strikingly, we found that 67% of the mutants survived better than the susceptible bacteria in the intracellular niche of the phagocytic cells. In particular, all E. coli streptomycin-resistant mutants exhibited an intracellular advantage. On the other hand, 42% of the mutants incurred a high fitness cost when the bacteria were allowed to divide outside of macrophages. This study shows that single nonsynonymous changes affecting fundamental processes in the cell can contribute to prolonged survival of E. coli in the context of an infection. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-01 2013-01-01T00:00:00Z 2015-11-03T12:56:30Z |
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/10400.7/463 |
url |
http://hdl.handle.net/10400.7/463 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages Migla Miskinyte and Isabel Gordo Antimicrob. Agents Chemother. January 2013 57:1 189-195; Accepted manuscript posted online 22 October 2012, doi:10.1128/AAC.01632-12 10.1128/AAC.01632-12 |
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.publisher.none.fl_str_mv |
American Society for Microbiology |
publisher.none.fl_str_mv |
American Society for Microbiology |
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 |
institution |
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) |
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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1799130572942999552 |