Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfection

Autores
Hernandez Morfa, Mirelys; Reinoso Vizcaino, Nicolas Martin; Zappia, Victoria Eugenia; Olivero, Nadia Belén; Cortes, Paulo R.; Stempin, Cinthia; Perez, Daniel R.; Echenique, Jose Ricardo
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Streptococcus pneumoniae is a major pathogen responsible for severe complications in patients with prior influenza A virus (IAV) infection. We have previously demonstrated that S. pneumoniae exhibits increased intracellular survival within IAV-infected cells. Fluoroquinolones (FQs) are widely used to treat pneumococcal infections. However, our prior work has shown that S. pneumoniae can develop intracellular FQ persistence, a phenomenon triggered by oxidative stress within host cells. This persistence allows the bacteria to withstand high FQ concentrations. In this study, we show that IAV infection enhances pneumococcal FQ persistence during intracellular survival within pneumocytes, macrophages, and neutrophils. This enhancement is partly due to increased oxidative stress induced by the viral infection. We find that this phenotype is particularly pronounced in autophagy-proficient host cells, potentially resulting from IAV-induced blockage of autophagosome-lysosome fusion. Moreover, we identified several S. pneumoniae genes involved in oxidative stress response that contribute to FQ persistence, including sodA (superoxide dismutase), clpL (chaperone), nrdH (glutaredoxin), and psaB (Mn+2 transporter component). Our findings reveal a novel mechanism of antibiotic persistence promoted by viral infection within host cells. This underscores the importance of considering this phenomenon when using FQs to treat pneumococcal infections, especially in patients with concurrent influenza A infection.
Fil: Hernandez Morfa, Mirelys. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Reinoso Vizcaino, Nicolas Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Zappia, Victoria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Olivero, Nadia Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Cortes, Paulo R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Stempin, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Perez, Daniel R.. College Of Veterinary Medicine ; University Of Georgia;
Fil: Echenique, Jose Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Materia
Streptococcus pneumoniae
autophagy
fluoroquinolones
influenza A
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/266839
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/266839
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfectionHernandez Morfa, MirelysReinoso Vizcaino, Nicolas MartinZappia, Victoria EugeniaOlivero, Nadia BelénCortes, Paulo R.Stempin, CinthiaPerez, Daniel R.Echenique, Jose RicardoStreptococcus pneumoniaeautophagyfluoroquinolonesinfluenza Ahttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Streptococcus pneumoniae is a major pathogen responsible for severe complications in patients with prior influenza A virus (IAV) infection. We have previously demonstrated that S. pneumoniae exhibits increased intracellular survival within IAV-infected cells. Fluoroquinolones (FQs) are widely used to treat pneumococcal infections. However, our prior work has shown that S. pneumoniae can develop intracellular FQ persistence, a phenomenon triggered by oxidative stress within host cells. This persistence allows the bacteria to withstand high FQ concentrations. In this study, we show that IAV infection enhances pneumococcal FQ persistence during intracellular survival within pneumocytes, macrophages, and neutrophils. This enhancement is partly due to increased oxidative stress induced by the viral infection. We find that this phenotype is particularly pronounced in autophagy-proficient host cells, potentially resulting from IAV-induced blockage of autophagosome-lysosome fusion. Moreover, we identified several S. pneumoniae genes involved in oxidative stress response that contribute to FQ persistence, including sodA (superoxide dismutase), clpL (chaperone), nrdH (glutaredoxin), and psaB (Mn+2 transporter component). Our findings reveal a novel mechanism of antibiotic persistence promoted by viral infection within host cells. This underscores the importance of considering this phenomenon when using FQs to treat pneumococcal infections, especially in patients with concurrent influenza A infection.Fil: Hernandez Morfa, Mirelys. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Reinoso Vizcaino, Nicolas Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Zappia, Victoria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Olivero, Nadia Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Cortes, Paulo R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Stempin, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Perez, Daniel R.. College Of Veterinary Medicine ; University Of Georgia;Fil: Echenique, Jose Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFrontiers Media2024-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266839Hernandez Morfa, Mirelys; Reinoso Vizcaino, Nicolas Martin; Zappia, Victoria Eugenia; Olivero, Nadia Belén; Cortes, Paulo R.; et al.; Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfection; Frontiers Media; Frontiers in Microbiology; 15; 7-2024; 1-121664-302XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fmicb.2024.1423995/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fmicb.2024.1423995info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:44:56Zoai:ri.conicet.gov.ar:11336/266839instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:44:56.801CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfection
title Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfection
spellingShingle Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfection
Hernandez Morfa, Mirelys
Streptococcus pneumoniae
autophagy
fluoroquinolones
influenza A
title_short Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfection
title_full Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfection
title_fullStr Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfection
title_full_unstemmed Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfection
title_sort Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfection
dc.creator.none.fl_str_mv Hernandez Morfa, Mirelys
Reinoso Vizcaino, Nicolas Martin
Zappia, Victoria Eugenia
Olivero, Nadia Belén
Cortes, Paulo R.
Stempin, Cinthia
Perez, Daniel R.
Echenique, Jose Ricardo
author Hernandez Morfa, Mirelys
author_facet Hernandez Morfa, Mirelys
Reinoso Vizcaino, Nicolas Martin
Zappia, Victoria Eugenia
Olivero, Nadia Belén
Cortes, Paulo R.
Stempin, Cinthia
Perez, Daniel R.
Echenique, Jose Ricardo
author_role author
author2 Reinoso Vizcaino, Nicolas Martin
Zappia, Victoria Eugenia
Olivero, Nadia Belén
Cortes, Paulo R.
Stempin, Cinthia
Perez, Daniel R.
Echenique, Jose Ricardo
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Streptococcus pneumoniae
autophagy
fluoroquinolones
influenza A
topic Streptococcus pneumoniae
autophagy
fluoroquinolones
influenza A
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Streptococcus pneumoniae is a major pathogen responsible for severe complications in patients with prior influenza A virus (IAV) infection. We have previously demonstrated that S. pneumoniae exhibits increased intracellular survival within IAV-infected cells. Fluoroquinolones (FQs) are widely used to treat pneumococcal infections. However, our prior work has shown that S. pneumoniae can develop intracellular FQ persistence, a phenomenon triggered by oxidative stress within host cells. This persistence allows the bacteria to withstand high FQ concentrations. In this study, we show that IAV infection enhances pneumococcal FQ persistence during intracellular survival within pneumocytes, macrophages, and neutrophils. This enhancement is partly due to increased oxidative stress induced by the viral infection. We find that this phenotype is particularly pronounced in autophagy-proficient host cells, potentially resulting from IAV-induced blockage of autophagosome-lysosome fusion. Moreover, we identified several S. pneumoniae genes involved in oxidative stress response that contribute to FQ persistence, including sodA (superoxide dismutase), clpL (chaperone), nrdH (glutaredoxin), and psaB (Mn+2 transporter component). Our findings reveal a novel mechanism of antibiotic persistence promoted by viral infection within host cells. This underscores the importance of considering this phenomenon when using FQs to treat pneumococcal infections, especially in patients with concurrent influenza A infection.
Fil: Hernandez Morfa, Mirelys. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Reinoso Vizcaino, Nicolas Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Zappia, Victoria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Olivero, Nadia Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Cortes, Paulo R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Stempin, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Perez, Daniel R.. College Of Veterinary Medicine ; University Of Georgia;
Fil: Echenique, Jose Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
description Streptococcus pneumoniae is a major pathogen responsible for severe complications in patients with prior influenza A virus (IAV) infection. We have previously demonstrated that S. pneumoniae exhibits increased intracellular survival within IAV-infected cells. Fluoroquinolones (FQs) are widely used to treat pneumococcal infections. However, our prior work has shown that S. pneumoniae can develop intracellular FQ persistence, a phenomenon triggered by oxidative stress within host cells. This persistence allows the bacteria to withstand high FQ concentrations. In this study, we show that IAV infection enhances pneumococcal FQ persistence during intracellular survival within pneumocytes, macrophages, and neutrophils. This enhancement is partly due to increased oxidative stress induced by the viral infection. We find that this phenotype is particularly pronounced in autophagy-proficient host cells, potentially resulting from IAV-induced blockage of autophagosome-lysosome fusion. Moreover, we identified several S. pneumoniae genes involved in oxidative stress response that contribute to FQ persistence, including sodA (superoxide dismutase), clpL (chaperone), nrdH (glutaredoxin), and psaB (Mn+2 transporter component). Our findings reveal a novel mechanism of antibiotic persistence promoted by viral infection within host cells. This underscores the importance of considering this phenomenon when using FQs to treat pneumococcal infections, especially in patients with concurrent influenza A infection.
publishDate 2024
dc.date.none.fl_str_mv 2024-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/266839
Hernandez Morfa, Mirelys; Reinoso Vizcaino, Nicolas Martin; Zappia, Victoria Eugenia; Olivero, Nadia Belén; Cortes, Paulo R.; et al.; Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfection; Frontiers Media; Frontiers in Microbiology; 15; 7-2024; 1-12
1664-302X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/266839
identifier_str_mv Hernandez Morfa, Mirelys; Reinoso Vizcaino, Nicolas Martin; Zappia, Victoria Eugenia; Olivero, Nadia Belén; Cortes, Paulo R.; et al.; Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfection; Frontiers Media; Frontiers in Microbiology; 15; 7-2024; 1-12
1664-302X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fmicb.2024.1423995/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fmicb.2024.1423995
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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