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Staphylococcus aureus Biofilm Growth on Cystic Fibrosis Airway Epithelial Cells Is Enhanced during Respiratory Syncytial Virus Coinfection

Staphylococcus aureus is a major cause of chronic respiratory infection in patients with cystic fibrosis (CF). We recently showed that Pseudomonas aeruginosa exhibits enhanced biofilm formation during respiratory syncytial virus (RSV) coinfection on human CF airway epithelial cells (AECs). The impac...

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Autores principales: Kiedrowski, Megan R., Gaston, Jordan R., Kocak, Brian R., Coburn, Stefanie L., Lee, Stella, Pilewski, Joseph M., Myerburg, Michael M., Bomberger, Jennifer M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094059/
https://www.ncbi.nlm.nih.gov/pubmed/30111629
http://dx.doi.org/10.1128/mSphere.00341-18
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author Kiedrowski, Megan R.
Gaston, Jordan R.
Kocak, Brian R.
Coburn, Stefanie L.
Lee, Stella
Pilewski, Joseph M.
Myerburg, Michael M.
Bomberger, Jennifer M.
author_facet Kiedrowski, Megan R.
Gaston, Jordan R.
Kocak, Brian R.
Coburn, Stefanie L.
Lee, Stella
Pilewski, Joseph M.
Myerburg, Michael M.
Bomberger, Jennifer M.
author_sort Kiedrowski, Megan R.
collection PubMed
description Staphylococcus aureus is a major cause of chronic respiratory infection in patients with cystic fibrosis (CF). We recently showed that Pseudomonas aeruginosa exhibits enhanced biofilm formation during respiratory syncytial virus (RSV) coinfection on human CF airway epithelial cells (AECs). The impact of respiratory viruses on other bacterial pathogens during polymicrobial infections in CF remains largely unknown. To investigate if S. aureus biofilm growth in the CF airways is impacted by virus coinfection, we evaluated S. aureus growth on CF AECs. Initial studies showed an increase in S. aureus growth over 24 h, and microscopy revealed biofilm-like clusters of bacteria on CF AECs. Biofilm growth was enhanced when CF AECs were coinfected with RSV, and this observation was confirmed with S. aureus CF clinical isolates. Apical conditioned medium from RSV-infected cells promoted S. aureus biofilms in the absence of the host epithelium, suggesting that a secreted factor produced during virus infection benefits S. aureus biofilms. Exogenous iron addition did not significantly alter biofilm formation, suggesting that it is not likely the secreted factor. We further characterized S. aureus-RSV coinfection in our model using dual host-pathogen RNA sequencing, allowing us to observe specific contributions of S. aureus and RSV to the host response during coinfection. Using the dual host-pathogen RNA sequencing approach, we observed increased availability of nutrients from the host and upregulation of S. aureus genes involved in growth, protein translation and export, and amino acid metabolism during RSV coinfection. IMPORTANCE The airways of individuals with cystic fibrosis (CF) are commonly chronically infected, and Staphylococcus aureus is the dominant bacterial respiratory pathogen in CF children. CF patients also experience frequent respiratory virus infections, and it has been hypothesized that virus coinfection increases the severity of S. aureus lung infections in CF. We investigated the relationship between S. aureus and the CF airway epithelium and observed that coinfection with respiratory syncytial virus (RSV) enhances S. aureus biofilm growth. However, iron, which was previously found to be a significant factor influencing Pseudomonas aeruginosa biofilms during virus coinfection, plays a minor role in S. aureus coinfections. Transcriptomic analyses provided new insight into how bacterial and viral pathogens alter host defense and suggest potential pathways by which dampening of host responses to one pathogen may favor persistence of another in the CF airways, highlighting complex interactions occurring between bacteria, viruses, and the host during polymicrobial infections.
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spelling pubmed-60940592018-08-16 Staphylococcus aureus Biofilm Growth on Cystic Fibrosis Airway Epithelial Cells Is Enhanced during Respiratory Syncytial Virus Coinfection Kiedrowski, Megan R. Gaston, Jordan R. Kocak, Brian R. Coburn, Stefanie L. Lee, Stella Pilewski, Joseph M. Myerburg, Michael M. Bomberger, Jennifer M. mSphere Research Article Staphylococcus aureus is a major cause of chronic respiratory infection in patients with cystic fibrosis (CF). We recently showed that Pseudomonas aeruginosa exhibits enhanced biofilm formation during respiratory syncytial virus (RSV) coinfection on human CF airway epithelial cells (AECs). The impact of respiratory viruses on other bacterial pathogens during polymicrobial infections in CF remains largely unknown. To investigate if S. aureus biofilm growth in the CF airways is impacted by virus coinfection, we evaluated S. aureus growth on CF AECs. Initial studies showed an increase in S. aureus growth over 24 h, and microscopy revealed biofilm-like clusters of bacteria on CF AECs. Biofilm growth was enhanced when CF AECs were coinfected with RSV, and this observation was confirmed with S. aureus CF clinical isolates. Apical conditioned medium from RSV-infected cells promoted S. aureus biofilms in the absence of the host epithelium, suggesting that a secreted factor produced during virus infection benefits S. aureus biofilms. Exogenous iron addition did not significantly alter biofilm formation, suggesting that it is not likely the secreted factor. We further characterized S. aureus-RSV coinfection in our model using dual host-pathogen RNA sequencing, allowing us to observe specific contributions of S. aureus and RSV to the host response during coinfection. Using the dual host-pathogen RNA sequencing approach, we observed increased availability of nutrients from the host and upregulation of S. aureus genes involved in growth, protein translation and export, and amino acid metabolism during RSV coinfection. IMPORTANCE The airways of individuals with cystic fibrosis (CF) are commonly chronically infected, and Staphylococcus aureus is the dominant bacterial respiratory pathogen in CF children. CF patients also experience frequent respiratory virus infections, and it has been hypothesized that virus coinfection increases the severity of S. aureus lung infections in CF. We investigated the relationship between S. aureus and the CF airway epithelium and observed that coinfection with respiratory syncytial virus (RSV) enhances S. aureus biofilm growth. However, iron, which was previously found to be a significant factor influencing Pseudomonas aeruginosa biofilms during virus coinfection, plays a minor role in S. aureus coinfections. Transcriptomic analyses provided new insight into how bacterial and viral pathogens alter host defense and suggest potential pathways by which dampening of host responses to one pathogen may favor persistence of another in the CF airways, highlighting complex interactions occurring between bacteria, viruses, and the host during polymicrobial infections. American Society for Microbiology 2018-08-15 /pmc/articles/PMC6094059/ /pubmed/30111629 http://dx.doi.org/10.1128/mSphere.00341-18 Text en Copyright © 2018 Kiedrowski et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Kiedrowski, Megan R.
Gaston, Jordan R.
Kocak, Brian R.
Coburn, Stefanie L.
Lee, Stella
Pilewski, Joseph M.
Myerburg, Michael M.
Bomberger, Jennifer M.
Staphylococcus aureus Biofilm Growth on Cystic Fibrosis Airway Epithelial Cells Is Enhanced during Respiratory Syncytial Virus Coinfection
title Staphylococcus aureus Biofilm Growth on Cystic Fibrosis Airway Epithelial Cells Is Enhanced during Respiratory Syncytial Virus Coinfection
title_full Staphylococcus aureus Biofilm Growth on Cystic Fibrosis Airway Epithelial Cells Is Enhanced during Respiratory Syncytial Virus Coinfection
title_fullStr Staphylococcus aureus Biofilm Growth on Cystic Fibrosis Airway Epithelial Cells Is Enhanced during Respiratory Syncytial Virus Coinfection
title_full_unstemmed Staphylococcus aureus Biofilm Growth on Cystic Fibrosis Airway Epithelial Cells Is Enhanced during Respiratory Syncytial Virus Coinfection
title_short Staphylococcus aureus Biofilm Growth on Cystic Fibrosis Airway Epithelial Cells Is Enhanced during Respiratory Syncytial Virus Coinfection
title_sort staphylococcus aureus biofilm growth on cystic fibrosis airway epithelial cells is enhanced during respiratory syncytial virus coinfection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094059/
https://www.ncbi.nlm.nih.gov/pubmed/30111629
http://dx.doi.org/10.1128/mSphere.00341-18
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