Attenuation of in vitro host-pathogen interactions in quinolone-resistant Salmonella Typhi mutants

Objectives The relationship between quinolone resistance acquisition and invasion impairment has been studied in some Salmonella enterica serovars. However, little information has been reported regarding the invasive human-restricted pathogen Salmonella Typhi. The aim of this study was to investigat...

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Autores: Ballesté Delpierre, Clara Celia, Fàbrega Santamaria, Anna, Ferrer Navarro, Mario, Mathur, Ramkumar, Ghosh, Sankar, Vila Estapé, Jordi
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/107171
Acceso en línea:https://hdl.handle.net/2445/107171
Access Level:acceso abierto
Palabra clave:Salmonel·la
Quinolones
Mutació (Biologia)
Antibiòtics
Salmonella
Quinolone antibacterial agents
Mutation (Biology)
Antibiotics
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spelling Attenuation of in vitro host-pathogen interactions in quinolone-resistant Salmonella Typhi mutantsBallesté Delpierre, Clara CeliaFàbrega Santamaria, AnnaFerrer Navarro, MarioMathur, RamkumarGhosh, SankarVila Estapé, JordiSalmonel·laQuinolonesMutació (Biologia)AntibiòticsSalmonellaQuinolone antibacterial agentsMutation (Biology)AntibioticsObjectives The relationship between quinolone resistance acquisition and invasion impairment has been studied in some Salmonella enterica serovars. However, little information has been reported regarding the invasive human-restricted pathogen Salmonella Typhi. The aim of this study was to investigate the molecular mechanisms of quinolone resistance acquisition and its impact on virulence in this serovar. Methods Two antibiotic-resistant mutants (Ty_c1 and Ty_c2) were generated from a Salmonella Typhi clinical isolate (Ty_wt). The three strains were compared in terms of antimicrobial susceptibility, molecular mechanisms of resistance, gene expression of virulence-related factors, ability to invade eukaryotic cells (human epithelial cells and macrophages) and cytokine production. Results Multidrug resistance in Ty_c2 was attributed to AcrAB/TolC overproduction, decreased OmpF (both mediated by the mar regulon) and decreased OmpC. The two mutants showed a gradually reduced expression of virulence-related genes (invA, hilA, hilD, fliC and fimA), correlating with decreased motility, reduced infection of HeLa cells and impaired uptake by and intracellular survival in human macrophages. Moreover, Ty_c2 also showed reduced tviA expression. Additionally, we revealed a significant reduction in TNF-α and IL-1β production and decreased NF-κB activation. Conclusions In this study, we provide an in-depth characterization of the molecular mechanisms of antibiotic resistance in the Salmonella Typhi serovar and evidence that acquisition of antimicrobial resistance is concomitantly detected with a loss of virulence (epithelial cell invasion, macrophage phagocytosis and cytokine production). We suggest that the low prevalence of clinical isolates of Salmonella Typhi highly resistant to ciprofloxacin is due to poor immunogenicity and impaired dissemination ability of these isolates.Oxford University Press2017201720162017info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion12 p.application/pdfhttps://hdl.handle.net/2445/107171Articles publicats en revistes (Fonaments Clínics)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1093/jac/dkv299Journal of Antimicrobial Chemotherapy, 2016, vol. 71, num. 1, p. 111-122https://doi.org/10.1093/jac/dkv299(c) Ballesté Delpierre, Clara Celia et al., 2016info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1071712026-05-29T05:05:01Z
dc.title.none.fl_str_mv Attenuation of in vitro host-pathogen interactions in quinolone-resistant Salmonella Typhi mutants
title Attenuation of in vitro host-pathogen interactions in quinolone-resistant Salmonella Typhi mutants
spellingShingle Attenuation of in vitro host-pathogen interactions in quinolone-resistant Salmonella Typhi mutants
Ballesté Delpierre, Clara Celia
Salmonel·la
Quinolones
Mutació (Biologia)
Antibiòtics
Salmonella
Quinolone antibacterial agents
Mutation (Biology)
Antibiotics
title_short Attenuation of in vitro host-pathogen interactions in quinolone-resistant Salmonella Typhi mutants
title_full Attenuation of in vitro host-pathogen interactions in quinolone-resistant Salmonella Typhi mutants
title_fullStr Attenuation of in vitro host-pathogen interactions in quinolone-resistant Salmonella Typhi mutants
title_full_unstemmed Attenuation of in vitro host-pathogen interactions in quinolone-resistant Salmonella Typhi mutants
title_sort Attenuation of in vitro host-pathogen interactions in quinolone-resistant Salmonella Typhi mutants
dc.creator.none.fl_str_mv Ballesté Delpierre, Clara Celia
Fàbrega Santamaria, Anna
Ferrer Navarro, Mario
Mathur, Ramkumar
Ghosh, Sankar
Vila Estapé, Jordi
author Ballesté Delpierre, Clara Celia
author_facet Ballesté Delpierre, Clara Celia
Fàbrega Santamaria, Anna
Ferrer Navarro, Mario
Mathur, Ramkumar
Ghosh, Sankar
Vila Estapé, Jordi
author_role author
author2 Fàbrega Santamaria, Anna
Ferrer Navarro, Mario
Mathur, Ramkumar
Ghosh, Sankar
Vila Estapé, Jordi
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Salmonel·la
Quinolones
Mutació (Biologia)
Antibiòtics
Salmonella
Quinolone antibacterial agents
Mutation (Biology)
Antibiotics
topic Salmonel·la
Quinolones
Mutació (Biologia)
Antibiòtics
Salmonella
Quinolone antibacterial agents
Mutation (Biology)
Antibiotics
description Objectives The relationship between quinolone resistance acquisition and invasion impairment has been studied in some Salmonella enterica serovars. However, little information has been reported regarding the invasive human-restricted pathogen Salmonella Typhi. The aim of this study was to investigate the molecular mechanisms of quinolone resistance acquisition and its impact on virulence in this serovar. Methods Two antibiotic-resistant mutants (Ty_c1 and Ty_c2) were generated from a Salmonella Typhi clinical isolate (Ty_wt). The three strains were compared in terms of antimicrobial susceptibility, molecular mechanisms of resistance, gene expression of virulence-related factors, ability to invade eukaryotic cells (human epithelial cells and macrophages) and cytokine production. Results Multidrug resistance in Ty_c2 was attributed to AcrAB/TolC overproduction, decreased OmpF (both mediated by the mar regulon) and decreased OmpC. The two mutants showed a gradually reduced expression of virulence-related genes (invA, hilA, hilD, fliC and fimA), correlating with decreased motility, reduced infection of HeLa cells and impaired uptake by and intracellular survival in human macrophages. Moreover, Ty_c2 also showed reduced tviA expression. Additionally, we revealed a significant reduction in TNF-α and IL-1β production and decreased NF-κB activation. Conclusions In this study, we provide an in-depth characterization of the molecular mechanisms of antibiotic resistance in the Salmonella Typhi serovar and evidence that acquisition of antimicrobial resistance is concomitantly detected with a loss of virulence (epithelial cell invasion, macrophage phagocytosis and cytokine production). We suggest that the low prevalence of clinical isolates of Salmonella Typhi highly resistant to ciprofloxacin is due to poor immunogenicity and impaired dissemination ability of these isolates.
publishDate 2016
dc.date.none.fl_str_mv 2016
2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/107171
url https://hdl.handle.net/2445/107171
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1093/jac/dkv299
Journal of Antimicrobial Chemotherapy, 2016, vol. 71, num. 1, p. 111-122
https://doi.org/10.1093/jac/dkv299
dc.rights.none.fl_str_mv (c) Ballesté Delpierre, Clara Celia et al., 2016
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Ballesté Delpierre, Clara Celia et al., 2016
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12 p.
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv Articles publicats en revistes (Fonaments Clínics)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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