The Effect of the Nasopharyngeal Microbiota on Pneumococcal Colonization and Pathogenesis in the Post-Pneumococcal Conjugate Vaccine Era
Reddinger, Ryan M.
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The development of secondary bacterial pneumonia following Influenza A Virus infection is a common and serious complication during both seasonal influenza, and pandemic outbreaks. This complication affects tens of thousands of individuals each year and is a significant source of both morbidity and mortality worldwide. These infections are often severe resulting in gross tissue damage, necrosis, the development of systemic disease and often death. The most common bacterial species involved in these infections are Staphylococcus aureus and Streptococcus pneumoniae . The phenomenon of secondary bacterial pneumonia is well established. Many elegant studies have shown that the colonizing strains of bacteria from the nasal tissue are the primary etiologic agents and that influenza modulated immune responses and tissue damage promote bacterial persistence in the lungs. Despite these findings, the mechanism of transition from colonization to invasive disease, a crucial step in pathogenesis, remained unexplored. The studies in this dissertation suggest that in response to changes in the host physiologic state associated with influenza A virus infection, S. aureus disperses from the biofilm and disseminates into the lungs causing pneumonia. When in a dual species biofilm with S. pneumoniae , S. aureus no longer responds to these same stimuli, while S. pneumoniae remains unaffected by the presence of co-colonizing S. aureus and readily causes invasive lung disease. These studies suggest that in a dual species biofilm, S. pneumoniae modulates the pathogenic abilities of S. aureus .