Modeling Klebsiella pneumoniae pathogenesis by infection of the wax moth Galleria mellonella

The implementation of infection models that approximate human disease is essential for understanding pathogenesis at the molecular level and for testing new therapies before they are entered into clinical stages. Insects are increasingly being used as surrogate hosts because they share, with mammals...

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Autores: Insua, José Luis, Llobet, Enrique, Moranta, David, Pérez Gutiérrez, Camino, Tomás, Anna, Garmendia García, Juncal, Bengoechea Alonso, José Antonio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Universidad Pública de Navarra
Repositorio:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/32076
Acceso en línea:https://hdl.handle.net/2454/32076
Access Level:acceso abierto
Palabra clave:Infection
Galleria mellonella
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spelling Modeling Klebsiella pneumoniae pathogenesis by infection of the wax moth Galleria mellonellaInsua, José LuisLlobet, EnriqueMoranta, DavidPérez Gutiérrez, CaminoTomás, AnnaGarmendia García, JuncalBengoechea Alonso, José AntonioInfectionGalleria mellonellaThe implementation of infection models that approximate human disease is essential for understanding pathogenesis at the molecular level and for testing new therapies before they are entered into clinical stages. Insects are increasingly being used as surrogate hosts because they share, with mammals, essential aspects of the innate immune response to infections. We examined whether the larva of the wax moth Galleria mellonella could be used as a host model to conceptually approximate Klebsiella pneumoniae-triggered pneumonia. We report that the G. mellonella model is capable of distinguishing between pathogenic and nonpathogenic Klebsiella strains. Moreover, K. pneumoniae infection of G. mellonella models some of the known features of Klebsiella-induced pneumonia, i.e., cell death associated with bacterial replication, avoidance of phagocytosis by phagocytes, and the attenuation of host defense responses, chiefly the production of antimicrobial factors. Similar to the case for the mouse pneumonia model, activation of innate responses improved G. mellonella survival against subsequent Klebsiella challenge. Virulence factors necessary in the mouse pneumonia model were also implicated in the Galleria model. We found that mutants lacking capsule polysaccharide, lipid A decorations, or the outer membrane proteins OmpA and OmpK36 were attenuated in Galleria. All mutants activated G. mellonella defensive responses. The Galleria model also allowed us to monitor Klebsiella gene expression. The expression levels of cps and the loci implicated in lipid A remodeling peaked during the first hours postinfection, in a PhoPQ- and PmrAB-governed process. Taken together, these results support the utility of G. mellonella as a surrogate host for assessing infections with K. pneumoniae.Fellowship support to J.L.I. from the Conselleria d'Educació, Cultura i Universitats Govern Illes Balears (cofunded by the European Regional Development Fund) is gratefully acknowledged. Part of this work was supported by grants from the Biomedicine Program of the Ministerio de Economía y Competitividad (grants SAF2009-07885 and SAF2012-39841) to J.A.B. The Laboratory of Microbial Pathogenesis is supported by a grant to competitive groups (project reference 46/2011) from the Conselleria d'Educació, Cultura i Universitats Govern Illes Balears (cofunded by the European Regional Development Fund). CIBERES is an initiative from the Instituto de Salud Carlos III.American Society for MicrobiologyIdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua2013info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2454/32076reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarrainstname:Universidad Pública de NavarraInglés© 2013, American Society for Microbiology. All Rights Reserved.info:eu-repo/semantics/openAccessoai:academica-e.unavarra.es:2454/320762026-06-17T12:41:47Z
dc.title.none.fl_str_mv Modeling Klebsiella pneumoniae pathogenesis by infection of the wax moth Galleria mellonella
title Modeling Klebsiella pneumoniae pathogenesis by infection of the wax moth Galleria mellonella
spellingShingle Modeling Klebsiella pneumoniae pathogenesis by infection of the wax moth Galleria mellonella
Insua, José Luis
Infection
Galleria mellonella
title_short Modeling Klebsiella pneumoniae pathogenesis by infection of the wax moth Galleria mellonella
title_full Modeling Klebsiella pneumoniae pathogenesis by infection of the wax moth Galleria mellonella
title_fullStr Modeling Klebsiella pneumoniae pathogenesis by infection of the wax moth Galleria mellonella
title_full_unstemmed Modeling Klebsiella pneumoniae pathogenesis by infection of the wax moth Galleria mellonella
title_sort Modeling Klebsiella pneumoniae pathogenesis by infection of the wax moth Galleria mellonella
dc.creator.none.fl_str_mv Insua, José Luis
Llobet, Enrique
Moranta, David
Pérez Gutiérrez, Camino
Tomás, Anna
Garmendia García, Juncal
Bengoechea Alonso, José Antonio
author Insua, José Luis
author_facet Insua, José Luis
Llobet, Enrique
Moranta, David
Pérez Gutiérrez, Camino
Tomás, Anna
Garmendia García, Juncal
Bengoechea Alonso, José Antonio
author_role author
author2 Llobet, Enrique
Moranta, David
Pérez Gutiérrez, Camino
Tomás, Anna
Garmendia García, Juncal
Bengoechea Alonso, José Antonio
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua
dc.subject.none.fl_str_mv Infection
Galleria mellonella
topic Infection
Galleria mellonella
description The implementation of infection models that approximate human disease is essential for understanding pathogenesis at the molecular level and for testing new therapies before they are entered into clinical stages. Insects are increasingly being used as surrogate hosts because they share, with mammals, essential aspects of the innate immune response to infections. We examined whether the larva of the wax moth Galleria mellonella could be used as a host model to conceptually approximate Klebsiella pneumoniae-triggered pneumonia. We report that the G. mellonella model is capable of distinguishing between pathogenic and nonpathogenic Klebsiella strains. Moreover, K. pneumoniae infection of G. mellonella models some of the known features of Klebsiella-induced pneumonia, i.e., cell death associated with bacterial replication, avoidance of phagocytosis by phagocytes, and the attenuation of host defense responses, chiefly the production of antimicrobial factors. Similar to the case for the mouse pneumonia model, activation of innate responses improved G. mellonella survival against subsequent Klebsiella challenge. Virulence factors necessary in the mouse pneumonia model were also implicated in the Galleria model. We found that mutants lacking capsule polysaccharide, lipid A decorations, or the outer membrane proteins OmpA and OmpK36 were attenuated in Galleria. All mutants activated G. mellonella defensive responses. The Galleria model also allowed us to monitor Klebsiella gene expression. The expression levels of cps and the loci implicated in lipid A remodeling peaked during the first hours postinfection, in a PhoPQ- and PmrAB-governed process. Taken together, these results support the utility of G. mellonella as a surrogate host for assessing infections with K. pneumoniae.
publishDate 2013
dc.date.none.fl_str_mv 2013
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 https://hdl.handle.net/2454/32076
url https://hdl.handle.net/2454/32076
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv © 2013, American Society for Microbiology. All Rights Reserved.
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © 2013, American Society for Microbiology. All Rights Reserved.
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:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
instname:Universidad Pública de Navarra
instname_str Universidad Pública de Navarra
reponame_str Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
collection Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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