Klebsiella pneumoniae ST258 negatively regulates the oxidative burst in human neutrophils

Autores
Castillo, Luis A.; Birnberg-Weiss, Federico; Rodriguez-Rodrigues, Nahuel; Martire-Greco, Daiana; Bigi, Fabiana; Landoni, Veronica I.; Gomez, Sonia A.; Fernandez, Gabriela C.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The epidemic clone of Klebsiella pneumoniae (Kpn), sequence type 258 (ST258), carbapenamase producer (KPC), commonly infects hospitalized patients that are left with scarce therapeutic option since carbapenems are last resort antibiotics for life-threatening bacterial infections. To improve prevention and treatment, we should better understand the biology of Kpn KPC ST258 infections. Our hypothesis was that Kpn KPC ST258 evade the first line of defense of innate immunity, the polymorphonuclear neutrophil (PMN), by decreasing its functional response. Therefore, our aim was to evaluate how the ST258 Kpn clone affects PMN responses, focusing on the respiratory burst, compared to another opportunistic pathogen, Escherichia coli (Eco). We found that Kpn KPC ST258 was unable to trigger bactericidal responses as reactive oxygen species (ROS) generation and NETosis, compared to the high induction observed with Eco, but both bacterial strains were similarly phagocytized and cause increases in cell size and CD11b expression. The absence of ROS induction was also observed with other Kpn ST258 strains negative for KPC. These results reflect certain selectivity in terms of the functions that are triggered in PMN by Kpn, which seems to evade specifically those responses critical for bacterial survival. In this sense, bactericidal mechanisms evasion was associated with a higher survival of Kpn KPC ST258 compared to Eco. To investigate the mechanisms and molecules involved in ROS inhibition, we used bacterial extracts (BE) and found that BE were able to inhibit ROS generation triggered by the well-known ROS inducer, fMLP. A sequence of experiments led us to elucidate that the polysaccharide part of LPS was responsible for this inhibition, whereas lipid A mediated the other responses that were not affected by bacteria, such as cell size increase and CD11b up-regulation. In conclusion, we unraveled a mechanism of immune evasion of Kpn KPC ST258, which may contribute to design more effective strategies for the treatment of these multi-resistant bacterial infections.
Instituto de Biotecnología
Fil: Castillo, Luis A. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; Argentina
Fil: Birnberg-Weiss, Federico. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; Argentina
Fil: Rodriguez-Rodrigues, Nahuel. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; Argentina
Fil: Martire-Greco, Daiana. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; Argentina
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; Argentina
Fil: Landoni, Veronica I. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; Argentina
Fil: Gomez, Sonia A. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas Dr. Carlos G. Malbrán. Servicio de Antimicrobianos; Argentina
Fil: Fernandez, Gabriela C. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; Argentina
Fuente
Frontiers in Immunology 10 : 929. (2019 Apr 26)
Materia
Klebsiella Pneumoniae
Neutrófilos
Respuesta Inmunológica
Neutrophils
Immune Response
Human Neutrophils
LPS
Respiratory Burst
Neutrófilos Humanos
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/6094
Acceder
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oai_identifier_str oai:localhost:20.500.12123/6094
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network_name_str INTA Digital (INTA)
spelling Klebsiella pneumoniae ST258 negatively regulates the oxidative burst in human neutrophilsCastillo, Luis A.Birnberg-Weiss, FedericoRodriguez-Rodrigues, NahuelMartire-Greco, DaianaBigi, FabianaLandoni, Veronica I.Gomez, Sonia A.Fernandez, Gabriela C.Klebsiella PneumoniaeNeutrófilosRespuesta InmunológicaNeutrophilsImmune ResponseHuman NeutrophilsLPSRespiratory BurstNeutrófilos HumanosThe epidemic clone of Klebsiella pneumoniae (Kpn), sequence type 258 (ST258), carbapenamase producer (KPC), commonly infects hospitalized patients that are left with scarce therapeutic option since carbapenems are last resort antibiotics for life-threatening bacterial infections. To improve prevention and treatment, we should better understand the biology of Kpn KPC ST258 infections. Our hypothesis was that Kpn KPC ST258 evade the first line of defense of innate immunity, the polymorphonuclear neutrophil (PMN), by decreasing its functional response. Therefore, our aim was to evaluate how the ST258 Kpn clone affects PMN responses, focusing on the respiratory burst, compared to another opportunistic pathogen, Escherichia coli (Eco). We found that Kpn KPC ST258 was unable to trigger bactericidal responses as reactive oxygen species (ROS) generation and NETosis, compared to the high induction observed with Eco, but both bacterial strains were similarly phagocytized and cause increases in cell size and CD11b expression. The absence of ROS induction was also observed with other Kpn ST258 strains negative for KPC. These results reflect certain selectivity in terms of the functions that are triggered in PMN by Kpn, which seems to evade specifically those responses critical for bacterial survival. In this sense, bactericidal mechanisms evasion was associated with a higher survival of Kpn KPC ST258 compared to Eco. To investigate the mechanisms and molecules involved in ROS inhibition, we used bacterial extracts (BE) and found that BE were able to inhibit ROS generation triggered by the well-known ROS inducer, fMLP. A sequence of experiments led us to elucidate that the polysaccharide part of LPS was responsible for this inhibition, whereas lipid A mediated the other responses that were not affected by bacteria, such as cell size increase and CD11b up-regulation. In conclusion, we unraveled a mechanism of immune evasion of Kpn KPC ST258, which may contribute to design more effective strategies for the treatment of these multi-resistant bacterial infections.Instituto de BiotecnologíaFil: Castillo, Luis A. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; ArgentinaFil: Birnberg-Weiss, Federico. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; ArgentinaFil: Rodriguez-Rodrigues, Nahuel. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; ArgentinaFil: Martire-Greco, Daiana. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; ArgentinaFil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; ArgentinaFil: Landoni, Veronica I. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; ArgentinaFil: Gomez, Sonia A. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas Dr. Carlos G. Malbrán. Servicio de Antimicrobianos; ArgentinaFil: Fernandez, Gabriela C. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; ArgentinaFrontiers Media2019-10-11T11:18:44Z2019-10-11T11:18:44Z2019-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://www.frontiersin.org/articles/10.3389/fimmu.2019.00929/fullhttp://hdl.handle.net/20.500.12123/60941664-3224https://doi.org/10.3389/fimmu.2019.00929Frontiers in Immunology 10 : 929. (2019 Apr 26)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-09-29T13:44:48Zoai:localhost:20.500.12123/6094instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-29 13:44:48.281INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Klebsiella pneumoniae ST258 negatively regulates the oxidative burst in human neutrophils
title Klebsiella pneumoniae ST258 negatively regulates the oxidative burst in human neutrophils
spellingShingle Klebsiella pneumoniae ST258 negatively regulates the oxidative burst in human neutrophils
Castillo, Luis A.
Klebsiella Pneumoniae
Neutrófilos
Respuesta Inmunológica
Neutrophils
Immune Response
Human Neutrophils
LPS
Respiratory Burst
Neutrófilos Humanos
title_short Klebsiella pneumoniae ST258 negatively regulates the oxidative burst in human neutrophils
title_full Klebsiella pneumoniae ST258 negatively regulates the oxidative burst in human neutrophils
title_fullStr Klebsiella pneumoniae ST258 negatively regulates the oxidative burst in human neutrophils
title_full_unstemmed Klebsiella pneumoniae ST258 negatively regulates the oxidative burst in human neutrophils
title_sort Klebsiella pneumoniae ST258 negatively regulates the oxidative burst in human neutrophils
dc.creator.none.fl_str_mv Castillo, Luis A.
Birnberg-Weiss, Federico
Rodriguez-Rodrigues, Nahuel
Martire-Greco, Daiana
Bigi, Fabiana
Landoni, Veronica I.
Gomez, Sonia A.
Fernandez, Gabriela C.
author Castillo, Luis A.
author_facet Castillo, Luis A.
Birnberg-Weiss, Federico
Rodriguez-Rodrigues, Nahuel
Martire-Greco, Daiana
Bigi, Fabiana
Landoni, Veronica I.
Gomez, Sonia A.
Fernandez, Gabriela C.
author_role author
author2 Birnberg-Weiss, Federico
Rodriguez-Rodrigues, Nahuel
Martire-Greco, Daiana
Bigi, Fabiana
Landoni, Veronica I.
Gomez, Sonia A.
Fernandez, Gabriela C.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Klebsiella Pneumoniae
Neutrófilos
Respuesta Inmunológica
Neutrophils
Immune Response
Human Neutrophils
LPS
Respiratory Burst
Neutrófilos Humanos
topic Klebsiella Pneumoniae
Neutrófilos
Respuesta Inmunológica
Neutrophils
Immune Response
Human Neutrophils
LPS
Respiratory Burst
Neutrófilos Humanos
dc.description.none.fl_txt_mv The epidemic clone of Klebsiella pneumoniae (Kpn), sequence type 258 (ST258), carbapenamase producer (KPC), commonly infects hospitalized patients that are left with scarce therapeutic option since carbapenems are last resort antibiotics for life-threatening bacterial infections. To improve prevention and treatment, we should better understand the biology of Kpn KPC ST258 infections. Our hypothesis was that Kpn KPC ST258 evade the first line of defense of innate immunity, the polymorphonuclear neutrophil (PMN), by decreasing its functional response. Therefore, our aim was to evaluate how the ST258 Kpn clone affects PMN responses, focusing on the respiratory burst, compared to another opportunistic pathogen, Escherichia coli (Eco). We found that Kpn KPC ST258 was unable to trigger bactericidal responses as reactive oxygen species (ROS) generation and NETosis, compared to the high induction observed with Eco, but both bacterial strains were similarly phagocytized and cause increases in cell size and CD11b expression. The absence of ROS induction was also observed with other Kpn ST258 strains negative for KPC. These results reflect certain selectivity in terms of the functions that are triggered in PMN by Kpn, which seems to evade specifically those responses critical for bacterial survival. In this sense, bactericidal mechanisms evasion was associated with a higher survival of Kpn KPC ST258 compared to Eco. To investigate the mechanisms and molecules involved in ROS inhibition, we used bacterial extracts (BE) and found that BE were able to inhibit ROS generation triggered by the well-known ROS inducer, fMLP. A sequence of experiments led us to elucidate that the polysaccharide part of LPS was responsible for this inhibition, whereas lipid A mediated the other responses that were not affected by bacteria, such as cell size increase and CD11b up-regulation. In conclusion, we unraveled a mechanism of immune evasion of Kpn KPC ST258, which may contribute to design more effective strategies for the treatment of these multi-resistant bacterial infections.
Instituto de Biotecnología
Fil: Castillo, Luis A. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; Argentina
Fil: Birnberg-Weiss, Federico. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; Argentina
Fil: Rodriguez-Rodrigues, Nahuel. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; Argentina
Fil: Martire-Greco, Daiana. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; Argentina
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; Argentina
Fil: Landoni, Veronica I. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; Argentina
Fil: Gomez, Sonia A. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas Dr. Carlos G. Malbrán. Servicio de Antimicrobianos; Argentina
Fil: Fernandez, Gabriela C. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; Argentina
description The epidemic clone of Klebsiella pneumoniae (Kpn), sequence type 258 (ST258), carbapenamase producer (KPC), commonly infects hospitalized patients that are left with scarce therapeutic option since carbapenems are last resort antibiotics for life-threatening bacterial infections. To improve prevention and treatment, we should better understand the biology of Kpn KPC ST258 infections. Our hypothesis was that Kpn KPC ST258 evade the first line of defense of innate immunity, the polymorphonuclear neutrophil (PMN), by decreasing its functional response. Therefore, our aim was to evaluate how the ST258 Kpn clone affects PMN responses, focusing on the respiratory burst, compared to another opportunistic pathogen, Escherichia coli (Eco). We found that Kpn KPC ST258 was unable to trigger bactericidal responses as reactive oxygen species (ROS) generation and NETosis, compared to the high induction observed with Eco, but both bacterial strains were similarly phagocytized and cause increases in cell size and CD11b expression. The absence of ROS induction was also observed with other Kpn ST258 strains negative for KPC. These results reflect certain selectivity in terms of the functions that are triggered in PMN by Kpn, which seems to evade specifically those responses critical for bacterial survival. In this sense, bactericidal mechanisms evasion was associated with a higher survival of Kpn KPC ST258 compared to Eco. To investigate the mechanisms and molecules involved in ROS inhibition, we used bacterial extracts (BE) and found that BE were able to inhibit ROS generation triggered by the well-known ROS inducer, fMLP. A sequence of experiments led us to elucidate that the polysaccharide part of LPS was responsible for this inhibition, whereas lipid A mediated the other responses that were not affected by bacteria, such as cell size increase and CD11b up-regulation. In conclusion, we unraveled a mechanism of immune evasion of Kpn KPC ST258, which may contribute to design more effective strategies for the treatment of these multi-resistant bacterial infections.
publishDate 2019
dc.date.none.fl_str_mv 2019-10-11T11:18:44Z
2019-10-11T11:18:44Z
2019-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://www.frontiersin.org/articles/10.3389/fimmu.2019.00929/full
http://hdl.handle.net/20.500.12123/6094
1664-3224
https://doi.org/10.3389/fimmu.2019.00929
url https://www.frontiersin.org/articles/10.3389/fimmu.2019.00929/full
http://hdl.handle.net/20.500.12123/6094
https://doi.org/10.3389/fimmu.2019.00929
identifier_str_mv 1664-3224
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Frontiers in Immunology 10 : 929. (2019 Apr 26)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
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instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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