Klebsiella pneumoniae ST258 impairs intracellular elastase mobilization and persists within human neutrophils

Klebsiella pneumoniae (Kp) strains of sequence type (ST) 258 producing K. pneumoniae-carbapenemase (KPC) are a major cause of hospital-associated outbreaks and the main contributors of carbapenemase spreading. Here, we deepen into the mechanisms behind the inhibition of neutrophil bactericidal funct...

Descripción completa

Detalles Bibliográficos
Autores principales: Birnberg-Weiss, Federico, Castro, Joselyn E., Pittaluga, Jose R., Castillo, Luis A., Martire-Greco, Daiana, Fuentes, Federico, Bigi, Fabiana, Gomez, Sonia A., Landoni, Veronica I., Fernandez, Gabriela C.
Formato: info:ar-repo/semantics/artículo
Lenguaje:Inglés
Publicado: Elsevier 2025
Materias:
Acceso en línea:http://hdl.handle.net/20.500.12123/21502
https://www.sciencedirect.com/science/article/abs/pii/S0944501324004361
https://doi.org/10.1016/j.micres.2024.128035
_version_ 1855038411523489792
author Birnberg-Weiss, Federico
Castro, Joselyn E.
Pittaluga, Jose R.
Castillo, Luis A.
Martire-Greco, Daiana
Fuentes, Federico
Bigi, Fabiana
Gomez, Sonia A.
Landoni, Veronica I.
Fernandez, Gabriela C.
author_browse Bigi, Fabiana
Birnberg-Weiss, Federico
Castillo, Luis A.
Castro, Joselyn E.
Fernandez, Gabriela C.
Fuentes, Federico
Gomez, Sonia A.
Landoni, Veronica I.
Martire-Greco, Daiana
Pittaluga, Jose R.
author_facet Birnberg-Weiss, Federico
Castro, Joselyn E.
Pittaluga, Jose R.
Castillo, Luis A.
Martire-Greco, Daiana
Fuentes, Federico
Bigi, Fabiana
Gomez, Sonia A.
Landoni, Veronica I.
Fernandez, Gabriela C.
author_sort Birnberg-Weiss, Federico
collection INTA Digital
description Klebsiella pneumoniae (Kp) strains of sequence type (ST) 258 producing K. pneumoniae-carbapenemase (KPC) are a major cause of hospital-associated outbreaks and the main contributors of carbapenemase spreading. Here, we deepen into the mechanisms behind the inhibition of neutrophil bactericidal functions mediated by a clinical isolate of Kp ST258 KPC, Kp from now on. We found that NETs formation induced by different stimuli (PMA, ionomycin, Staphylococcus aureus) was significantly reduced in the presence of Kp. We revealed that Kp affects actin polymerization which correlates with impaired mobilization of elastase from azurophilic granules to the nucleus and reduced elastase mobilization towards phagosomes that contain bacteria. In line with these results, Kp survived within neutrophils for 3 h post-challenge without compromising neutrophil viability. We also found that different Kp clinical isolates inhibited NETs formation and actin polymerization. These results describe a strategy of evasion used by Kp to subvert PMN-mediating both intra and extracellular mechanisms of killing, representing a clear advantage for the survival and spreading of this multidrug-resistant bacteria.
format info:ar-repo/semantics/artículo
id INTA21502
institution Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina)
language Inglés
publishDate 2025
publishDateRange 2025
publishDateSort 2025
publisher Elsevier
publisherStr Elsevier
record_format dspace
spelling INTA215022025-02-28T10:56:50Z Klebsiella pneumoniae ST258 impairs intracellular elastase mobilization and persists within human neutrophils Birnberg-Weiss, Federico Castro, Joselyn E. Pittaluga, Jose R. Castillo, Luis A. Martire-Greco, Daiana Fuentes, Federico Bigi, Fabiana Gomez, Sonia A. Landoni, Veronica I. Fernandez, Gabriela C. Klebsiella pneumoniae Neutrófilos Neutrophils Klebsiella pneumoniae (Kp) strains of sequence type (ST) 258 producing K. pneumoniae-carbapenemase (KPC) are a major cause of hospital-associated outbreaks and the main contributors of carbapenemase spreading. Here, we deepen into the mechanisms behind the inhibition of neutrophil bactericidal functions mediated by a clinical isolate of Kp ST258 KPC, Kp from now on. We found that NETs formation induced by different stimuli (PMA, ionomycin, Staphylococcus aureus) was significantly reduced in the presence of Kp. We revealed that Kp affects actin polymerization which correlates with impaired mobilization of elastase from azurophilic granules to the nucleus and reduced elastase mobilization towards phagosomes that contain bacteria. In line with these results, Kp survived within neutrophils for 3 h post-challenge without compromising neutrophil viability. We also found that different Kp clinical isolates inhibited NETs formation and actin polymerization. These results describe a strategy of evasion used by Kp to subvert PMN-mediating both intra and extracellular mechanisms of killing, representing a clear advantage for the survival and spreading of this multidrug-resistant bacteria. Instituto de Biotecnología Fil: Birnberg-Weiss, Federico. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina Fil: Birnberg-Weiss, Federico. Consejo Nacional de investigaciones Científicas y Técnicas; Argentina Fil: Castro, Joselyn E. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina Fil: Castro, Joselyn E. Consejo Nacional de investigaciones Científicas y Técnicas; Argentina Fil: Pittaluga, Jose R. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina Fil: Pittaluga, Jose R. Consejo Nacional de investigaciones Científicas y Técnicas; Argentina Fil: Castillo, Luis A. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina Fil: Castillo, Luis A. Consejo Nacional de investigaciones Científicas y Técnicas; Argentina Fil: Martire-Greco, Daiana. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina Fil: Martire-Greco, Daiana. Consejo Nacional de investigaciones Científicas y Técnicas; Argentina Fil: Fuentes, Federico. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina Fil: Fuentes, Federico. Consejo Nacional de investigaciones Científicas y Técnicas; Argentina Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Bigi, Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas; 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: Gomez, Sonia A. Consejo Nacional de investigaciones Científicas y Técnicas; Argentina Fil: Landoni, Veronica I. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina Fil: Landoni, Veronica I. Consejo Nacional de investigaciones Científicas y Técnicas; Argentina Fil: Fernandez, Gabriela C. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental. Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina Fil: Fernandez, Gabriela C. Consejo Nacional de investigaciones Científicas y Técnicas; Argentina 2025-02-28T10:49:59Z 2025-02-28T10:49:59Z 2025-03 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/21502 https://www.sciencedirect.com/science/article/abs/pii/S0944501324004361 1618-0623 0944-5013 https://doi.org/10.1016/j.micres.2024.128035 eng info:eu-repo/semantics/restrictedAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf Elsevier Microbiological Research 292 : 128035 (March 2025)
spellingShingle Klebsiella pneumoniae
Neutrófilos
Neutrophils
Birnberg-Weiss, Federico
Castro, Joselyn E.
Pittaluga, Jose R.
Castillo, Luis A.
Martire-Greco, Daiana
Fuentes, Federico
Bigi, Fabiana
Gomez, Sonia A.
Landoni, Veronica I.
Fernandez, Gabriela C.
Klebsiella pneumoniae ST258 impairs intracellular elastase mobilization and persists within human neutrophils
title Klebsiella pneumoniae ST258 impairs intracellular elastase mobilization and persists within human neutrophils
title_full Klebsiella pneumoniae ST258 impairs intracellular elastase mobilization and persists within human neutrophils
title_fullStr Klebsiella pneumoniae ST258 impairs intracellular elastase mobilization and persists within human neutrophils
title_full_unstemmed Klebsiella pneumoniae ST258 impairs intracellular elastase mobilization and persists within human neutrophils
title_short Klebsiella pneumoniae ST258 impairs intracellular elastase mobilization and persists within human neutrophils
title_sort klebsiella pneumoniae st258 impairs intracellular elastase mobilization and persists within human neutrophils
topic Klebsiella pneumoniae
Neutrófilos
Neutrophils
url http://hdl.handle.net/20.500.12123/21502
https://www.sciencedirect.com/science/article/abs/pii/S0944501324004361
https://doi.org/10.1016/j.micres.2024.128035
work_keys_str_mv AT birnbergweissfederico klebsiellapneumoniaest258impairsintracellularelastasemobilizationandpersistswithinhumanneutrophils
AT castrojoselyne klebsiellapneumoniaest258impairsintracellularelastasemobilizationandpersistswithinhumanneutrophils
AT pittalugajoser klebsiellapneumoniaest258impairsintracellularelastasemobilizationandpersistswithinhumanneutrophils
AT castilloluisa klebsiellapneumoniaest258impairsintracellularelastasemobilizationandpersistswithinhumanneutrophils
AT martiregrecodaiana klebsiellapneumoniaest258impairsintracellularelastasemobilizationandpersistswithinhumanneutrophils
AT fuentesfederico klebsiellapneumoniaest258impairsintracellularelastasemobilizationandpersistswithinhumanneutrophils
AT bigifabiana klebsiellapneumoniaest258impairsintracellularelastasemobilizationandpersistswithinhumanneutrophils
AT gomezsoniaa klebsiellapneumoniaest258impairsintracellularelastasemobilizationandpersistswithinhumanneutrophils
AT landoniveronicai klebsiellapneumoniaest258impairsintracellularelastasemobilizationandpersistswithinhumanneutrophils
AT fernandezgabrielac klebsiellapneumoniaest258impairsintracellularelastasemobilizationandpersistswithinhumanneutrophils