Characterization of influenza A viruses-methicillin-resistant Staphylococcus aureus co-infections at the alveolar-capillary barrier
| dc.contributor.author | Nickol, Michaela | |
| dc.contributor.examiningcommittee | Drebot, Michael (Medical Microbiology and Infectious Diseases) West, Adrian ( Physiology and Pathophysiology) | en_US |
| dc.contributor.supervisor | Kindrachuk, Jason (Medical Microbiology and Infectious Diseases) Keynan, Yoav (Medical Microbiology and Infectious Diseases) | en_US |
| dc.date.accessioned | 2020-01-08T20:46:52Z | |
| dc.date.available | 2020-01-08T20:46:52Z | |
| dc.date.issued | 2019 | en_US |
| dc.date.submitted | 2019-12-31T20:22:32Z | en |
| dc.degree.discipline | Medical Microbiology and Infectious Diseases | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | Influenza viruses have posed a threat to public health in the form of seasonal epidemics and sporadic pandemics for centuries, despite an intensive vaccine program and the existence of antivirals. Moreover, it is widely known that secondary bacterial co-infections are able to complicate influenza infections, resulting in increased morbidity and mortality. Secondary bacterial pathogens include Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae. However, Staphylococcus aureus, specifically methicillin-resistant S. aureus (MRSA) remains one of the most commonly seen secondary bacterial pathogens in influenza infections. In the case of influenza-bacterial co-infections, these pathogens are able to colonize the alveolar-capillary barrier, where the respiratory epithelial cells of the alveoli are in close proximity to the pulmonary endothelial cells of the capillary, allowing for gas exchange in the lungs. The breakdown of the alveolar-capillary barrier results in severe disease, hypoxemia, and fluid leakage. It is believed that this severe disease is the result of a combination of host-, viral-, and bacterial-mediated responses. However, there is a paucity of information regarding the mechanisms underlying influenza-bacterial co-infection pathogenesis. To further our understanding of severe disease pathogenesis, a co-culture model of the alveolar-capillary barrier was created using primary alveolar respiratory epithelial cells and pulmonary microvascular endothelial cells. This model was used to study modulation of MRSA’s replication kinetics and bacterial virulence factors in the presence of IAV. Additionally, the host response to influenza- MRSA co-infection was studied by measuring alveolar-capillary barrier integrity, the host kinome, and cytokine expression. We found that alveolar-capillary barrier disruption during co- infection is mediated primarily through host response dysregulation, resulting in the loss of alveolar-capillary barrier integrity. | en_US |
| dc.description.note | February 2020 | en_US |
| dc.identifier.citation | Nickol ME, Ciric J, Falcinelli S, Chertow DS, 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(2) | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/34462 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Influenza | en_US |
| dc.subject | Methicillin-Resistant Staphylococcus aureus | en_US |
| dc.subject | Co-infections | en_US |
| dc.subject | Alveolar-capillary barrier | en_US |
| dc.title | Characterization of influenza A viruses-methicillin-resistant Staphylococcus aureus co-infections at the alveolar-capillary barrier | en_US |
| dc.type | master thesis | en_US |