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Open AccessArticle

Characterization of Host and Bacterial Contributions to Lung Barrier Dysfunction Following Co-infection with 2009 Pandemic Influenza and Methicillin Resistant Staphylococcus aureus

1
Laboratory of Emerging and Re-Emerging Viruses, Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
2
Department of Microbiology and Immunology, University of North Carolina Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA
3
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
4
Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD 20892, USA
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(2), 116; https://doi.org/10.3390/v11020116
Received: 16 January 2019 / Accepted: 26 January 2019 / Published: 29 January 2019
(This article belongs to the Special Issue CSV2018: The 2nd symposium of the Canadian Society for Virology (CSV))
Influenza viruses are a threat to global public health resulting in ~500,000 deaths each year. Despite an intensive vaccination program, influenza infections remain a recurrent, yet unsolved public health problem. Secondary bacterial infections frequently complicate influenza infections during seasonal outbreaks and pandemics, resulting in increased morbidity and mortality. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is frequently associated with these co-infections, including the 2009 influenza pandemic. Damage to alveolar epithelium is a major contributor to severe influenza-bacterial co-infections and can result in gas exchange abnormalities, fluid leakage, and respiratory insufficiency. These deleterious manifestations likely involve both pathogen- and host-mediated mechanisms. However, there is a paucity of information regarding the mechanisms (pathogen- and/or host-mediated) underlying influenza-bacterial co-infection pathogenesis. To address this, we characterized the contributions of viral-, bacterial-, and host-mediated factors to the altered structure and function of alveolar epithelial cells during co-infection with a focus on the 2009 pandemic influenza (pdm2009) and MRSA. Here, we characterized pdm2009 and MRSA replication kinetics, temporal host kinome responses, modulation of MRSA virulence factors, and disruption of alveolar barrier integrity in response to pdm2009-MRSA co-infection. Our results suggest that alveolar barrier disruption during co-infection is mediated primarily through host response dysregulation, resulting in loss of alveolar barrier integrity. View Full-Text
Keywords: influenza; Staphylococcus aureus; co-infection; 2009 pandemic; alveolar epithelial cells; kinome; virulence factors; barrier function influenza; Staphylococcus aureus; co-infection; 2009 pandemic; alveolar epithelial cells; kinome; virulence factors; barrier function
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MDPI and ACS Style

Nickol, M.E.; Ciric, J.; Falcinelli, S.D.; Chertow, D.S.; Kindrachuk, J. Characterization of Host and Bacterial Contributions to Lung Barrier Dysfunction Following Co-infection with 2009 Pandemic Influenza and Methicillin Resistant Staphylococcus aureus. Viruses 2019, 11, 116.

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