Abundance of the Quorum-Sensing Factor Ax21 in Four Strains of Stenotrophomonas maltophilia Correlates with Mortality Rate in a New Zebrafish Model of Infection

Stenotrophomonas maltophilia is a Gram-negative pathogen with emerging nosocomial incidence. Little is known about its pathogenesis and the genomic diversity exhibited by clinical isolates complicates the study of pathogenicity and virulence factors. Here, we present a strategy to identify such fact...

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Autores: Ferrer-Navarro, Mario|||0000-0001-9990-914X, Planell Cerezo, Raquel|||0009-0003-9513-0245, Yero, Daniel|||0000-0002-6234-4082, Mongiardini, Elías, Torrent, Gerard, Huedo Moreno, Pol|||0000-0002-2933-0586, Martínez, Paula|||0000-0002-4655-5672, Roher Armentia, Nerea|||0000-0002-6659-4038, Mackenzie, Simon|||0000-0003-1845-6826, Gibert, Isidre|||0000-0003-1442-2258, Daura i Ribera, Xavier|||0000-0001-9235-6730
Tipo de recurso: artículo
Fecha de publicación:2013
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:112531
Acceso en línea:https://ddd.uab.cat/record/112531
https://dx.doi.org/urn:doi:10.1371/journal.pone.0067207
Access Level:acceso abierto
Palabra clave:Bacterial pathogens
Pathogenesis
Stenotrophomonas maltophilia
Zebrafish
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spelling Abundance of the Quorum-Sensing Factor Ax21 in Four Strains of Stenotrophomonas maltophilia Correlates with Mortality Rate in a New Zebrafish Model of InfectionFerrer-Navarro, Mario|||0000-0001-9990-914XPlanell Cerezo, Raquel|||0009-0003-9513-0245Yero, Daniel|||0000-0002-6234-4082Mongiardini, ElíasTorrent, GerardHuedo Moreno, Pol|||0000-0002-2933-0586Martínez, Paula|||0000-0002-4655-5672Roher Armentia, Nerea|||0000-0002-6659-4038Mackenzie, Simon|||0000-0003-1845-6826Gibert, Isidre|||0000-0003-1442-2258Daura i Ribera, Xavier|||0000-0001-9235-6730Bacterial pathogensPathogenesisStenotrophomonas maltophiliaZebrafishStenotrophomonas maltophilia is a Gram-negative pathogen with emerging nosocomial incidence. Little is known about its pathogenesis and the genomic diversity exhibited by clinical isolates complicates the study of pathogenicity and virulence factors. Here, we present a strategy to identify such factors in new clinical isolates of S. maltophilia, incorporating an adult-zebrafish model of S. maltophilia infection to evaluate relative virulence coupled to 2D difference gel electrophoresis to explore underlying differences in protein expression. In this study we report upon three recent clinical isolates and use the collection strain ATCC13637 as a reference. The adult-zebrafish model shows discrimination capacity, i.e. from very low to very high mortality rates, with clinical symptoms very similar to those observed in natural S. maltophilia infections in fish. Strain virulence correlates with resistance to human serum, in agreement with previous studies in mouse and rat and therefore supporting zebrafish as a replacement model. Despite its clinical origin, the collection strain ATCC13637 showed obvious signs of attenuation in zebrafish, with null mortality. Multilocus-sequence-typing analysis revealed that the most virulent strains, UV74 and M30, exhibit the strongest genetic similitude. Differential proteomic analysis led to the identification of 38 proteins with significantly different abundance in the three clinical strains relative to the reference strain. Orthologs of several of these proteins have been already reported to have a role in pathogenesis, virulence or resistance mechanisms thus supporting our strategy. Proof of concept is further provided by protein Ax21, whose abundance is shown here to be directly proportional to mortality in the zebrafish infection model. Indeed, recent studies have demonstrated that this protein is a quorum-sensing-related virulence factor. 22013-01-0120132013-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/112531https://dx.doi.org/urn:doi:10.1371/journal.pone.0067207reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengEuropean Commission https://doi.org/10.13039/501100000780 223101Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 BFU2010-17199Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2009/SGR-00108open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/2.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1125312026-06-06T12:50:31Z
dc.title.none.fl_str_mv Abundance of the Quorum-Sensing Factor Ax21 in Four Strains of Stenotrophomonas maltophilia Correlates with Mortality Rate in a New Zebrafish Model of Infection
title Abundance of the Quorum-Sensing Factor Ax21 in Four Strains of Stenotrophomonas maltophilia Correlates with Mortality Rate in a New Zebrafish Model of Infection
spellingShingle Abundance of the Quorum-Sensing Factor Ax21 in Four Strains of Stenotrophomonas maltophilia Correlates with Mortality Rate in a New Zebrafish Model of Infection
Ferrer-Navarro, Mario|||0000-0001-9990-914X
Bacterial pathogens
Pathogenesis
Stenotrophomonas maltophilia
Zebrafish
title_short Abundance of the Quorum-Sensing Factor Ax21 in Four Strains of Stenotrophomonas maltophilia Correlates with Mortality Rate in a New Zebrafish Model of Infection
title_full Abundance of the Quorum-Sensing Factor Ax21 in Four Strains of Stenotrophomonas maltophilia Correlates with Mortality Rate in a New Zebrafish Model of Infection
title_fullStr Abundance of the Quorum-Sensing Factor Ax21 in Four Strains of Stenotrophomonas maltophilia Correlates with Mortality Rate in a New Zebrafish Model of Infection
title_full_unstemmed Abundance of the Quorum-Sensing Factor Ax21 in Four Strains of Stenotrophomonas maltophilia Correlates with Mortality Rate in a New Zebrafish Model of Infection
title_sort Abundance of the Quorum-Sensing Factor Ax21 in Four Strains of Stenotrophomonas maltophilia Correlates with Mortality Rate in a New Zebrafish Model of Infection
dc.creator.none.fl_str_mv Ferrer-Navarro, Mario|||0000-0001-9990-914X
Planell Cerezo, Raquel|||0009-0003-9513-0245
Yero, Daniel|||0000-0002-6234-4082
Mongiardini, Elías
Torrent, Gerard
Huedo Moreno, Pol|||0000-0002-2933-0586
Martínez, Paula|||0000-0002-4655-5672
Roher Armentia, Nerea|||0000-0002-6659-4038
Mackenzie, Simon|||0000-0003-1845-6826
Gibert, Isidre|||0000-0003-1442-2258
Daura i Ribera, Xavier|||0000-0001-9235-6730
author Ferrer-Navarro, Mario|||0000-0001-9990-914X
author_facet Ferrer-Navarro, Mario|||0000-0001-9990-914X
Planell Cerezo, Raquel|||0009-0003-9513-0245
Yero, Daniel|||0000-0002-6234-4082
Mongiardini, Elías
Torrent, Gerard
Huedo Moreno, Pol|||0000-0002-2933-0586
Martínez, Paula|||0000-0002-4655-5672
Roher Armentia, Nerea|||0000-0002-6659-4038
Mackenzie, Simon|||0000-0003-1845-6826
Gibert, Isidre|||0000-0003-1442-2258
Daura i Ribera, Xavier|||0000-0001-9235-6730
author_role author
author2 Planell Cerezo, Raquel|||0009-0003-9513-0245
Yero, Daniel|||0000-0002-6234-4082
Mongiardini, Elías
Torrent, Gerard
Huedo Moreno, Pol|||0000-0002-2933-0586
Martínez, Paula|||0000-0002-4655-5672
Roher Armentia, Nerea|||0000-0002-6659-4038
Mackenzie, Simon|||0000-0003-1845-6826
Gibert, Isidre|||0000-0003-1442-2258
Daura i Ribera, Xavier|||0000-0001-9235-6730
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Bacterial pathogens
Pathogenesis
Stenotrophomonas maltophilia
Zebrafish
topic Bacterial pathogens
Pathogenesis
Stenotrophomonas maltophilia
Zebrafish
description Stenotrophomonas maltophilia is a Gram-negative pathogen with emerging nosocomial incidence. Little is known about its pathogenesis and the genomic diversity exhibited by clinical isolates complicates the study of pathogenicity and virulence factors. Here, we present a strategy to identify such factors in new clinical isolates of S. maltophilia, incorporating an adult-zebrafish model of S. maltophilia infection to evaluate relative virulence coupled to 2D difference gel electrophoresis to explore underlying differences in protein expression. In this study we report upon three recent clinical isolates and use the collection strain ATCC13637 as a reference. The adult-zebrafish model shows discrimination capacity, i.e. from very low to very high mortality rates, with clinical symptoms very similar to those observed in natural S. maltophilia infections in fish. Strain virulence correlates with resistance to human serum, in agreement with previous studies in mouse and rat and therefore supporting zebrafish as a replacement model. Despite its clinical origin, the collection strain ATCC13637 showed obvious signs of attenuation in zebrafish, with null mortality. Multilocus-sequence-typing analysis revealed that the most virulent strains, UV74 and M30, exhibit the strongest genetic similitude. Differential proteomic analysis led to the identification of 38 proteins with significantly different abundance in the three clinical strains relative to the reference strain. Orthologs of several of these proteins have been already reported to have a role in pathogenesis, virulence or resistance mechanisms thus supporting our strategy. Proof of concept is further provided by protein Ax21, whose abundance is shown here to be directly proportional to mortality in the zebrafish infection model. Indeed, recent studies have demonstrated that this protein is a quorum-sensing-related virulence factor.
publishDate 2013
dc.date.none.fl_str_mv 2
2013-01-01
2013
2013-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/112531
https://dx.doi.org/urn:doi:10.1371/journal.pone.0067207
url https://ddd.uab.cat/record/112531
https://dx.doi.org/urn:doi:10.1371/journal.pone.0067207
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission https://doi.org/10.13039/501100000780 223101
Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 BFU2010-17199
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2009/SGR-00108
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/2.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/2.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
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