Dissecting the mechanisms of linezolid resistance in a drosophila melanogaster infection model of staphylococcus aureus

Background. Mini-host models are simple experimental systems to study host-pathogen interactions. We adapted a Drosophila melanogaster infection model to evaluate the in vivo effect of different mechanisms of linezolid (LNZ) resistance in Staphylococcus aureus. Methods. Fly survival was evaluated af...

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Autores:
Diaz, Lorena
Kontoyiannis, Dimitrios P.
Panesso, Diana
Albert, Nathaniel D.
Singh, Kavindra V.
Tran, Truc T.
Munita, Jose M.
Murray, Barbara E.
Arias, Cesar A.
Tipo de recurso:
Article of journal
Fecha de publicación:
2013
Institución:
Universidad El Bosque
Repositorio:
Repositorio U. El Bosque
Idioma:
eng
OAI Identifier:
oai:repositorio.unbosque.edu.co:20.500.12495/4085
Acceso en línea:
http://hdl.handle.net/20.500.12495/4085
https://doi.org/10.1093/infdis/jit138
https://repositorio.unbosque.edu.co
Palabra clave:
Bacilos grampositivos formadores de endosporas
Acetamidas
Farmacorresistencia bacteriana
Staphylococcus aureus
Linezolid
Resistance
Drosophila melanogaster
Rights
openAccess
License
Acceso abierto
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oai_identifier_str oai:repositorio.unbosque.edu.co:20.500.12495/4085
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network_name_str Repositorio U. El Bosque
repository_id_str
dc.title.spa.fl_str_mv Dissecting the mechanisms of linezolid resistance in a drosophila melanogaster infection model of staphylococcus aureus
dc.title.translated.spa.fl_str_mv Dissecting the mechanisms of linezolid resistance in a drosophila melanogaster infection model of staphylococcus aureus
title Dissecting the mechanisms of linezolid resistance in a drosophila melanogaster infection model of staphylococcus aureus
spellingShingle Dissecting the mechanisms of linezolid resistance in a drosophila melanogaster infection model of staphylococcus aureus
Bacilos grampositivos formadores de endosporas
Acetamidas
Farmacorresistencia bacteriana
Staphylococcus aureus
Linezolid
Resistance
Drosophila melanogaster
title_short Dissecting the mechanisms of linezolid resistance in a drosophila melanogaster infection model of staphylococcus aureus
title_full Dissecting the mechanisms of linezolid resistance in a drosophila melanogaster infection model of staphylococcus aureus
title_fullStr Dissecting the mechanisms of linezolid resistance in a drosophila melanogaster infection model of staphylococcus aureus
title_full_unstemmed Dissecting the mechanisms of linezolid resistance in a drosophila melanogaster infection model of staphylococcus aureus
title_sort Dissecting the mechanisms of linezolid resistance in a drosophila melanogaster infection model of staphylococcus aureus
dc.creator.fl_str_mv Diaz, Lorena
Kontoyiannis, Dimitrios P.
Panesso, Diana
Albert, Nathaniel D.
Singh, Kavindra V.
Tran, Truc T.
Munita, Jose M.
Murray, Barbara E.
Arias, Cesar A.
dc.contributor.author.none.fl_str_mv Diaz, Lorena
Kontoyiannis, Dimitrios P.
Panesso, Diana
Albert, Nathaniel D.
Singh, Kavindra V.
Tran, Truc T.
Munita, Jose M.
Murray, Barbara E.
Arias, Cesar A.
dc.contributor.orcid.none.fl_str_mv Panesso, Diana [0000-0002-4049-9702]
dc.subject.decs.spa.fl_str_mv Bacilos grampositivos formadores de endosporas
Acetamidas
Farmacorresistencia bacteriana
topic Bacilos grampositivos formadores de endosporas
Acetamidas
Farmacorresistencia bacteriana
Staphylococcus aureus
Linezolid
Resistance
Drosophila melanogaster
dc.subject.keywords.spa.fl_str_mv Staphylococcus aureus
Linezolid
Resistance
Drosophila melanogaster
description Background. Mini-host models are simple experimental systems to study host-pathogen interactions. We adapted a Drosophila melanogaster infection model to evaluate the in vivo effect of different mechanisms of linezolid (LNZ) resistance in Staphylococcus aureus. Methods. Fly survival was evaluated after infection with LNZ-resistant S. aureus strains NRS119 (which has mutations in 23S ribosomal RNA [rRNA]), CM-05 and 004-737X (which carry cfr), LNZ-susceptible derivatives of CM-05 and 004-737X (which lack cfr), and ATCC 29213 (an LNZ-susceptible control). Flies were then fed food mixed with LNZ (concentration, 15–500 µg/mL). Results were compared to those in mouse peritonitis, using LNZ via oral gavage at 80 and 120 mg/kg every 12 hours. Results. LNZ at 500 µg/mL in fly food protected against all strains, while concentrations of 15–250 µg/mL failed to protect against NRS119 (survival, 1.6%–20%). An in vivo effect of cfr was only detected at concentrations of 30 and 15 µg/mL. In the mouse peritonitis model, LNZ (at doses that mimic human pharmacokinetics) protected mice from challenge with the cfr+ 004-737X strain but was ineffective against the NRS119 strain, which carried 23S rRNA mutations. Conclusions. The fly model offers promising advantages to dissect the in vivo effect of LNZ resistance in S. aureus, and findings from this model appear to be concordant with those from the mouse peritonitis model
publishDate 2013
dc.date.issued.none.fl_str_mv 2013
dc.date.accessioned.none.fl_str_mv 2020-09-14T22:08:06Z
dc.date.available.none.fl_str_mv 2020-09-14T22:08:06Z
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.local.none.fl_str_mv Artículo de revista
dc.type.coar.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
format http://purl.org/coar/resource_type/c_6501
dc.identifier.issn.none.fl_str_mv 1537-6613
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/20.500.12495/4085
dc.identifier.doi.none.fl_str_mv https://doi.org/10.1093/infdis/jit138
dc.identifier.instname.spa.fl_str_mv instname:Universidad El Bosque
dc.identifier.reponame.spa.fl_str_mv reponame:Repositorio Institucional Universidad El Bosque
dc.identifier.repourl.none.fl_str_mv https://repositorio.unbosque.edu.co
identifier_str_mv 1537-6613
instname:Universidad El Bosque
reponame:Repositorio Institucional Universidad El Bosque
url http://hdl.handle.net/20.500.12495/4085
https://doi.org/10.1093/infdis/jit138
https://repositorio.unbosque.edu.co
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.ispartofseries.spa.fl_str_mv Journal of Infectious Diseases, 1537-6613, Vol 208, Nro 1, 2013, pag 83-91
dc.relation.uri.none.fl_str_mv https://academic.oup.com/jid/article/208/1/83/796362
dc.rights.local.spa.fl_str_mv Acceso abierto
dc.rights.accessrights.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
info:eu-repo/semantics/openAccess
Acceso abierto
dc.rights.creativecommons.none.fl_str_mv 2013-07-01
rights_invalid_str_mv Acceso abierto
http://purl.org/coar/access_right/c_abf2
2013-07-01
eu_rights_str_mv openAccess
dc.format.mimetype.none.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Oxford University Press
dc.publisher.journal.spa.fl_str_mv Journal of Infectious Diseases
institution Universidad El Bosque
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spelling Diaz, LorenaKontoyiannis, Dimitrios P.Panesso, DianaAlbert, Nathaniel D.Singh, Kavindra V.Tran, Truc T.Munita, Jose M.Murray, Barbara E.Arias, Cesar A.Panesso, Diana [0000-0002-4049-9702]2020-09-14T22:08:06Z2020-09-14T22:08:06Z20131537-6613http://hdl.handle.net/20.500.12495/4085https://doi.org/10.1093/infdis/jit138instname:Universidad El Bosquereponame:Repositorio Institucional Universidad El Bosquehttps://repositorio.unbosque.edu.coapplication/pdfengOxford University PressJournal of Infectious DiseasesJournal of Infectious Diseases, 1537-6613, Vol 208, Nro 1, 2013, pag 83-91https://academic.oup.com/jid/article/208/1/83/796362Dissecting the mechanisms of linezolid resistance in a drosophila melanogaster infection model of staphylococcus aureusDissecting the mechanisms of linezolid resistance in a drosophila melanogaster infection model of staphylococcus aureusArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articlehttp://purl.org/coar/version/c_970fb48d4fbd8a85Bacilos grampositivos formadores de endosporasAcetamidasFarmacorresistencia bacterianaStaphylococcus aureusLinezolidResistanceDrosophila melanogasterBackground. Mini-host models are simple experimental systems to study host-pathogen interactions. We adapted a Drosophila melanogaster infection model to evaluate the in vivo effect of different mechanisms of linezolid (LNZ) resistance in Staphylococcus aureus. Methods. Fly survival was evaluated after infection with LNZ-resistant S. aureus strains NRS119 (which has mutations in 23S ribosomal RNA [rRNA]), CM-05 and 004-737X (which carry cfr), LNZ-susceptible derivatives of CM-05 and 004-737X (which lack cfr), and ATCC 29213 (an LNZ-susceptible control). Flies were then fed food mixed with LNZ (concentration, 15–500 µg/mL). Results were compared to those in mouse peritonitis, using LNZ via oral gavage at 80 and 120 mg/kg every 12 hours. Results. LNZ at 500 µg/mL in fly food protected against all strains, while concentrations of 15–250 µg/mL failed to protect against NRS119 (survival, 1.6%–20%). An in vivo effect of cfr was only detected at concentrations of 30 and 15 µg/mL. In the mouse peritonitis model, LNZ (at doses that mimic human pharmacokinetics) protected mice from challenge with the cfr+ 004-737X strain but was ineffective against the NRS119 strain, which carried 23S rRNA mutations. Conclusions. The fly model offers promising advantages to dissect the in vivo effect of LNZ resistance in S. aureus, and findings from this model appear to be concordant with those from the mouse peritonitis modelAcceso abiertohttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessAcceso abierto2013-07-01LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://repositorio.unbosque.edu.co/bitstreams/31a8f386-8781-44a5-ab46-1cf4c33c672f/download8a4605be74aa9ea9d79846c1fba20a33MD52THUMBNAILDíaz, Lorena_2013.pdf.jpgDíaz, Lorena_2013.pdf.jpgimage/jpeg5775https://repositorio.unbosque.edu.co/bitstreams/bb0b3a16-fd12-4194-ae1b-6e782e6a33d7/download7210a811635d1799e7c05fee5d259be7MD54ORIGINALDíaz, Lorena_2013.pdfDíaz, Lorena_2013.pdfapplication/pdf505350https://repositorio.unbosque.edu.co/bitstreams/44963041-ab47-48ed-a807-7eb820c3931d/downloadf6020e58a094e3f8811e4ebe737f364bMD53TEXTDíaz, Lorena_2013.pdf.txtDíaz, Lorena_2013.pdf.txtExtracted texttext/plain48155https://repositorio.unbosque.edu.co/bitstreams/26eec6c0-7c21-4af4-a1a2-fedfec6745e5/download9c52410f3e0d7249ae33497c5ae27333MD5520.500.12495/4085oai:repositorio.unbosque.edu.co:20.500.12495/40852024-02-07 02:55:20.823restrictedhttps://repositorio.unbosque.edu.coRepositorio Institucional Universidad El Bosquebibliotecas@biteca.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