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A multiomics analysis of direct interkingdom dynamics between influenza A virus and Streptococcus pneumoniae uncovers host-independent changes to bacterial virulence fitness

BACKGROUND: For almost a century, it has been recognized that influenza A virus (IAV) infection can promote the development of secondary bacterial infections (SBI) mainly caused by Streptococcus pneumoniae (Spn). Recent observations have shown that IAV is able to directly bind to the surface of Spn....

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Autores principales: Platt, Maryann P., Lin, Yi-Han, Penix, Trevor, Wiscovitch-Russo, Rosana, Vashee, Isha, Mares, Chris A., Rosch, Jason W., Yu, Yanbao, Gonzalez-Juarbe, Norberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815659/
https://www.ncbi.nlm.nih.gov/pubmed/36542660
http://dx.doi.org/10.1371/journal.ppat.1011020
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author Platt, Maryann P.
Lin, Yi-Han
Penix, Trevor
Wiscovitch-Russo, Rosana
Vashee, Isha
Mares, Chris A.
Rosch, Jason W.
Yu, Yanbao
Gonzalez-Juarbe, Norberto
author_facet Platt, Maryann P.
Lin, Yi-Han
Penix, Trevor
Wiscovitch-Russo, Rosana
Vashee, Isha
Mares, Chris A.
Rosch, Jason W.
Yu, Yanbao
Gonzalez-Juarbe, Norberto
author_sort Platt, Maryann P.
collection PubMed
description BACKGROUND: For almost a century, it has been recognized that influenza A virus (IAV) infection can promote the development of secondary bacterial infections (SBI) mainly caused by Streptococcus pneumoniae (Spn). Recent observations have shown that IAV is able to directly bind to the surface of Spn. To gain a foundational understanding of how direct IAV-Spn interaction alters bacterial biological fitness we employed combinatorial multiomic and molecular approaches. RESULTS: Here we show IAV significantly remodels the global transcriptome, proteome and phosphoproteome profiles of Spn independently of host effectors. We identified Spn surface proteins that interact with IAV proteins (hemagglutinin, nucleoprotein, and neuraminidase). In addition, IAV was found to directly modulate expression of Spn virulence determinants such as pneumococcal surface protein A, pneumolysin, and factors associated with antimicrobial resistance among many others. Metabolic pathways were significantly altered leading to changes in Spn growth rate. IAV was also found to drive Spn capsule shedding and the release of pneumococcal surface proteins. Released proteins were found to be involved in evasion of innate immune responses and actively reduced human complement hemolytic and opsonizing activity. IAV also led to phosphorylation changes in Spn proteins associated with metabolism and bacterial virulence. Validation of proteomic data showed significant changes in Spn galactose and glucose metabolism. Furthermore, supplementation with galactose rescued bacterial growth and promoted bacterial invasion, while glucose supplementation led to enhanced pneumolysin production and lung cell apoptosis. CONCLUSIONS: Here we demonstrate that IAV can directly modulate Spn biology without the requirement of host effectors and support the notion that inter-kingdom interactions between human viruses and commensal pathobionts can promote bacterial pathogenesis and microbiome dysbiosis.
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spelling pubmed-98156592023-01-06 A multiomics analysis of direct interkingdom dynamics between influenza A virus and Streptococcus pneumoniae uncovers host-independent changes to bacterial virulence fitness Platt, Maryann P. Lin, Yi-Han Penix, Trevor Wiscovitch-Russo, Rosana Vashee, Isha Mares, Chris A. Rosch, Jason W. Yu, Yanbao Gonzalez-Juarbe, Norberto PLoS Pathog Research Article BACKGROUND: For almost a century, it has been recognized that influenza A virus (IAV) infection can promote the development of secondary bacterial infections (SBI) mainly caused by Streptococcus pneumoniae (Spn). Recent observations have shown that IAV is able to directly bind to the surface of Spn. To gain a foundational understanding of how direct IAV-Spn interaction alters bacterial biological fitness we employed combinatorial multiomic and molecular approaches. RESULTS: Here we show IAV significantly remodels the global transcriptome, proteome and phosphoproteome profiles of Spn independently of host effectors. We identified Spn surface proteins that interact with IAV proteins (hemagglutinin, nucleoprotein, and neuraminidase). In addition, IAV was found to directly modulate expression of Spn virulence determinants such as pneumococcal surface protein A, pneumolysin, and factors associated with antimicrobial resistance among many others. Metabolic pathways were significantly altered leading to changes in Spn growth rate. IAV was also found to drive Spn capsule shedding and the release of pneumococcal surface proteins. Released proteins were found to be involved in evasion of innate immune responses and actively reduced human complement hemolytic and opsonizing activity. IAV also led to phosphorylation changes in Spn proteins associated with metabolism and bacterial virulence. Validation of proteomic data showed significant changes in Spn galactose and glucose metabolism. Furthermore, supplementation with galactose rescued bacterial growth and promoted bacterial invasion, while glucose supplementation led to enhanced pneumolysin production and lung cell apoptosis. CONCLUSIONS: Here we demonstrate that IAV can directly modulate Spn biology without the requirement of host effectors and support the notion that inter-kingdom interactions between human viruses and commensal pathobionts can promote bacterial pathogenesis and microbiome dysbiosis. Public Library of Science 2022-12-21 /pmc/articles/PMC9815659/ /pubmed/36542660 http://dx.doi.org/10.1371/journal.ppat.1011020 Text en © 2022 Platt et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Platt, Maryann P.
Lin, Yi-Han
Penix, Trevor
Wiscovitch-Russo, Rosana
Vashee, Isha
Mares, Chris A.
Rosch, Jason W.
Yu, Yanbao
Gonzalez-Juarbe, Norberto
A multiomics analysis of direct interkingdom dynamics between influenza A virus and Streptococcus pneumoniae uncovers host-independent changes to bacterial virulence fitness
title A multiomics analysis of direct interkingdom dynamics between influenza A virus and Streptococcus pneumoniae uncovers host-independent changes to bacterial virulence fitness
title_full A multiomics analysis of direct interkingdom dynamics between influenza A virus and Streptococcus pneumoniae uncovers host-independent changes to bacterial virulence fitness
title_fullStr A multiomics analysis of direct interkingdom dynamics between influenza A virus and Streptococcus pneumoniae uncovers host-independent changes to bacterial virulence fitness
title_full_unstemmed A multiomics analysis of direct interkingdom dynamics between influenza A virus and Streptococcus pneumoniae uncovers host-independent changes to bacterial virulence fitness
title_short A multiomics analysis of direct interkingdom dynamics between influenza A virus and Streptococcus pneumoniae uncovers host-independent changes to bacterial virulence fitness
title_sort multiomics analysis of direct interkingdom dynamics between influenza a virus and streptococcus pneumoniae uncovers host-independent changes to bacterial virulence fitness
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815659/
https://www.ncbi.nlm.nih.gov/pubmed/36542660
http://dx.doi.org/10.1371/journal.ppat.1011020
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