Quinolone Resistance Reversion by Targeting the SOS Response

Suppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of Escherichia coli representing multiple levels of quinolone resistance....

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Detalhes bibliográficos
Autores: Recacha, E., Machuca, J., Díaz Alba, P., Docobo Pérez, Fernando, Rodríguez Beltrán, Jerónimo, Rodríguez Martínez, José Manuel
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Recursos:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/65330
Acesso em linha:http://hdl.handle.net/11441/65330
https://doi.org/10.1128/mBio.00971-17
Access Level:acceso abierto
Palavra-chave:RecA
SOS response
quinolones
resensitization of antibiotic-resistant bacteria
resistance reversion
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repository_id_str
spelling Quinolone Resistance Reversion by Targeting the SOS ResponseRecacha, E.Machuca, J.Díaz Alba, P.Docobo Pérez, FernandoRodríguez Beltrán, JerónimoRodríguez Martínez, José ManuelRecASOS responsequinolonesresensitization of antibiotic-resistant bacteriaresistance reversionSuppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of Escherichia coli representing multiple levels of quinolone resistance. E. coli mutants exhibiting a spectrum of SOS activity were constructed from isogenic strains carrying quinolone resistance mechanisms with susceptible and resistant phenotypes. Changes in susceptibility were evaluated by static (MICs) and dynamic (killing curves or flow cytometry) methodologies. A peritoneal sepsis murine model was used to evaluate in vivo impact. Suppression of the SOS response was capable of resensitizing mutant strains with genes encoding three or four different resistance mechanisms (up to 15-fold reductions in MICs). Killing curve assays showed a clear disadvantage for survival (Δlog10 CFU per milliliter [CFU/ml] of 8 log units after 24 h), and the in vivo efficacy of ciprofloxacin was significantly enhanced (Δlog10 CFU/g of 1.76 log units) in resistant strains with a suppressed SOS response. This effect was evident even after short periods (60 min) of exposure. Suppression of the SOS response reverses antimicrobial resistance across a range of E. coli phenotypes from reduced susceptibility to highly resistant, playing a significant role in increasing the in vivo efficacy.American Society for MicrobiologyMicrobiología2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/11441/65330https://doi.org/10.1128/mBio.00971-17reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésmBio, 8 (5), 1-17.http://dx.doi.org/ 10.1128/mBio.00971-17info:eu-repo/semantics/openAccessoai:idus.us.es:11441/653302026-06-17T12:51:07Z
dc.title.none.fl_str_mv Quinolone Resistance Reversion by Targeting the SOS Response
title Quinolone Resistance Reversion by Targeting the SOS Response
spellingShingle Quinolone Resistance Reversion by Targeting the SOS Response
Recacha, E.
RecA
SOS response
quinolones
resensitization of antibiotic-resistant bacteria
resistance reversion
title_short Quinolone Resistance Reversion by Targeting the SOS Response
title_full Quinolone Resistance Reversion by Targeting the SOS Response
title_fullStr Quinolone Resistance Reversion by Targeting the SOS Response
title_full_unstemmed Quinolone Resistance Reversion by Targeting the SOS Response
title_sort Quinolone Resistance Reversion by Targeting the SOS Response
dc.creator.none.fl_str_mv Recacha, E.
Machuca, J.
Díaz Alba, P.
Docobo Pérez, Fernando
Rodríguez Beltrán, Jerónimo
Rodríguez Martínez, José Manuel
author Recacha, E.
author_facet Recacha, E.
Machuca, J.
Díaz Alba, P.
Docobo Pérez, Fernando
Rodríguez Beltrán, Jerónimo
Rodríguez Martínez, José Manuel
author_role author
author2 Machuca, J.
Díaz Alba, P.
Docobo Pérez, Fernando
Rodríguez Beltrán, Jerónimo
Rodríguez Martínez, José Manuel
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Microbiología
dc.subject.none.fl_str_mv RecA
SOS response
quinolones
resensitization of antibiotic-resistant bacteria
resistance reversion
topic RecA
SOS response
quinolones
resensitization of antibiotic-resistant bacteria
resistance reversion
description Suppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of Escherichia coli representing multiple levels of quinolone resistance. E. coli mutants exhibiting a spectrum of SOS activity were constructed from isogenic strains carrying quinolone resistance mechanisms with susceptible and resistant phenotypes. Changes in susceptibility were evaluated by static (MICs) and dynamic (killing curves or flow cytometry) methodologies. A peritoneal sepsis murine model was used to evaluate in vivo impact. Suppression of the SOS response was capable of resensitizing mutant strains with genes encoding three or four different resistance mechanisms (up to 15-fold reductions in MICs). Killing curve assays showed a clear disadvantage for survival (Δlog10 CFU per milliliter [CFU/ml] of 8 log units after 24 h), and the in vivo efficacy of ciprofloxacin was significantly enhanced (Δlog10 CFU/g of 1.76 log units) in resistant strains with a suppressed SOS response. This effect was evident even after short periods (60 min) of exposure. Suppression of the SOS response reverses antimicrobial resistance across a range of E. coli phenotypes from reduced susceptibility to highly resistant, playing a significant role in increasing the in vivo efficacy.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11441/65330
https://doi.org/10.1128/mBio.00971-17
url http://hdl.handle.net/11441/65330
https://doi.org/10.1128/mBio.00971-17
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv mBio, 8 (5), 1-17.
http://dx.doi.org/ 10.1128/mBio.00971-17
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
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:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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