Respiratory syncytial virus infection enhances Pseudomonas aeruginosa biofilm growth through dysregulation of nutritional immunity
Open accessAbstract
Clinical observations link respiratory virus infection and Pseudomonas aeruginosa colonization in chronic lung disease, including cystic fibrosis (CF) and chronic obstructive pulmonary disease. The development of P. aeruginosa into highly antibiotic-resistant biofilm communities promotes airway colonization and accounts for disease progression in patients. Although clinical studies show a strong correlation between CF patients' acquisition of chronic P. aeruginosa infections and respiratory virus infection, little is known about the mechanism by which chronic P. aeruginosa infections are initiated in the host. Using a coculture model to study the formation of bacterial biofilm formation associated with the airway epithelium, we show that respiratory viral infections and the induction of antiviral interferons promote robust secondary P. aeruginosa biofilm formation. We report that the induction of antiviral IFN signaling in response to respiratory syncytial virus (RSV) infection induces bacterial biofilm formation through a mechanism of dysregulated iron homeostasis of the airway epithelium. Moreover, increased apical release of the host iron-binding protein transferrin during RSV infection promotes P. aeruginosa biofilm development in vitro and in vivo. Thus, nutritional immunity pathways that are disrupted during respiratory viral infection create an environment that favors secondary bacterial infection and may provide previously unidentified targets to combat bacterial biofilm formation.
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Respiratory syncytial virus infection causes transferrin release, increasing available iron and promoting Pseudomonas aeruginosa infection and biofilm formation.
“Infection by respiratory syncytial virus causes transferrin release, increasing available iron and promoting P. aeruginosa infection and biofilm formation (61).”
From Transition Metals and Virulence in Bacteria (2016) · cites this paper as [61]
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Transition Metals and Virulence in Bacteria
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- Authors
- Hendricks, M. R., Lashua, L. P., Fischer, D. K., Flitter, B. A., Eichinger, K. M., Durbin, J. E., Sarkar, S. N., Coyne, C. B., Empey, K. M., & Bomberger, J. M.
- Affiliations
- University of Pittsburgh (US)
- Rutgers New Jersey Medical School (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-01-04
- Volume
- 113
- Issue
- 6
- Pages
- 1642-1647
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4760822
- OpenAlex
- W2231837916
- Cited by
- 168
- References
- 48
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 13 · 2023: 18 · 2022: 14 · 2021: 25 · 2020: 27 · 2019: 13 · 2018: 11 · 2017: 13 · 2016: 14
- FWCI
- 9.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | National Institutes of Health (R00HL098342, R01HL123771, P30DK072506, T32AI060525)
- Cystic Fibrosis Foundation (BOMBER14G0)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- respiratory syncytial virus, Pseudomonas aeruginosa, biofilm formation, nutritional immunity, iron homeostasis, interferon signaling, transferrin, airway epithelium, cystic fibrosis, chronic obstructive pulmonary disease, viral-bacterial coinfection, secondary bacterial infection, iron-binding proteins
- MeSH terms
- Animals, Antiviral Agents, Bronchi, Bronchoalveolar Lavage Fluid, Cystic Fibrosis, Epithelial Cells, Homeostasis, Humans, Immunity, Iron, Models, Biological, Nutritional Physiological Phenomena, Pseudomonas aeruginosa, Respiratory Syncytial Viruses, Transferrin, Signal Transduction, Interferon-beta, Respiratory Syncytial Virus Infections, Biofilms, Mice, Microbial Interactions
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