Scholarship & Research
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Item Initiation and pathogenesis of Staphylococcus aureus Pneumonia following influenza A infection(Montana State University - Bozeman, College of Letters & Science, 2019) Borgogna, Timothy Ryan; Chairperson, Graduate Committee: Jovanka Voyich-Kane; Adrian Sanchez-Gonzalez, Kelly Gorham and Jovanka M. Voyich were co-authors of the article, 'A precise pathogen delivery and recovery system for murine models of secondary bacterial pneumonia' in the journal 'JOVE Journal of visualized experiments' which is contained within this dissertation.; Bennett Hisey, Emily Heitman, Joshua J. Obar, Nicole Meissner and Jovanka M. Voyich were co-authors of the article, 'Secondary bacterial pneumonia by Staphylococcus aureus following influenza A infection is saeR/S dependent' in the journal 'Journal of infectious diseases' which is contained within this dissertation.; Madison M. Collins, Kyle A. Glose, Kyler B. Pallister, Tyler K. Pallister and Jovanka M. Voyich were co-authors of the article, 'Uncovering the executioner: disruption of pulmonary surfactant by influenza A triggers Staphylococcus aureus Pneumonia' which is contained within this dissertation.Infection influenza A virus (IAV) leads to increased host susceptibility to secondary bacterial pneumonia. In cases such as these, Staphylococcus aureus (S. aureus) has emerged as the dominant bacterial pathogen associated with severe infection outcomes. S. aureus is a common commensal of the anterior nares and is frequently trafficked into the lower respiratory tract through inhalations, micro-aspirations, and direct mucosal dispersion. Despite recurrent exposure to the lungs and the capacity to cause severe disease, cases of S. aureus pneumonia are rare in immunocompetent hosts. Previous efforts interrogating S. aureus secondary bacterial pneumonia have largely focused on the immunomodulation that occurs during the antecedent influenza infection and have ignored the virulence contributions of the bacterial pathogen. To that end, we developed a murine model of secondary pneumonia to investigate S. aureus pathogenesis following influenza A infection. We identify that secondary bacterial pneumonia by S. aureus is dependent on the activation of the two-component regulatory system (TCS) SaeR/S. Further, studies demonstrated that in the absence of IAV infection the healthy lung environment suppresses virulence gene expression. Characterization of the lung environment revealed that the lipid constituents of pulmonary surfactant suppress S. aureus virulence production. Our data provide a model of secondary bacterial pneumonia wherein infection with IAV significantly reduces surfactant lipid concentrations within the lungs. The reduction of pulmonary surfactant lipids leads to a loss of S. aureus virulence suppression and rapid activation of the major virulence regulator saeR/S. Taken together, these data provide a strong rational for the low incidence of primary S. aureus pneumonia and the increased severity of S. aureus pneumonia following antecedent influenza A infection. Furthermore, these data highlight possible pulmonary surfactant replacement therapies that may significantly alleviate secondary bacterial pneumonia morbidity and mortality.Item Assessing respiratory pathogen communities and demographic performance of bighorn sheep populations: a framework to develop management strategies for respiratory disease(Montana State University - Bozeman, College of Letters & Science, 2017) Butler, Carson Joseph; Chairperson, Graduate Committee: Robert A. GarrottRespiratory disease (pneumonia) is a persistent challenge for bighorn sheep (Ovis canadensis) conservation as sporadic epizootics cause up to 90% mortality in affected populations and are often followed by numerous years of low juvenile recruitment attributed to lamb pneumonia. Domestic sheep (Ovis aries) and domestic goats (Capra aegagrus hircus) are the origin of the disease and asymptomatically carry respiratory pathogens that cause respiratory disease when introduced to bighorn sheep. Pathogens that have been linked to respiratory disease in bighorn sheep include several species of bacteria in the Pasteurellaceae family and another bacterial species, Mycoplasma ovipneumoniae. Despite substantial efforts by management agencies to prevent contact between bighorn sheep and domestic sheep and goats, respiratory disease epizootics continue to affect bighorn sheep populations across much of their distribution with uncertain etiology. This study sought to investigate efficacy of diagnostic protocols in detecting Pasteurellaceae and Mycoplasma ovipneumoniae and generate sampling recommendations for different protocols, assess the distribution of these disease agents among 17 bighorn sheep populations in Montana and Wyoming and evaluate what associations existed between detection of these agents and demographic performance of bighorn sheep populations. Analysis of replicate samples from individual bighorn sheep revealed that detection probability for regularly-used diagnostic protocols was generally low (<50%) for Pasteurellaceae and was high (>70%) for Mycoplasma ovipneumoniae, suggesting that routine pathogen sampling likely mischaracterizes respiratory pathogen communities. Power analyses found that most pathogen species could be detected with 80% confidence at the population-level by conducting regularly-used protocols multiple times per animal. Each pathogen species was detected in over half of the study populations, and consideration of detection probability discerned that there was low confidence in negative test results for populations where the Pasteurellaceae species were not detected. 76% of study populations hosted Mycoplasma ovipneumoniae and Pasteurellaceae pathogens, yet a number of these populations were estimated to have positive population growth rates and recruitment rates greater than 30%. Overall, the results of this work suggest that bighorn sheep respiratory disease may be mitigated by manipulating population characteristics and respiratory disease epizootics could be caused by pathogens already resident in bighorn sheep populations.Item Effects of a primary influenza infection on susceptibility to a secondary Streptococcus pneumoniae infection(Montana State University - Bozeman, College of Agriculture, 2006) McNamee, Lynnelle Ann; Chairperson, Graduate Committee: Allen G. Harmsen.Influenza infections result in increased susceptibility to a secondary Streptococcus pneumoniae infection. The aim of the present studies was to determine the mechanism(s) responsible for this increase in susceptibility. Using an in vivo co-infection model, we found that susceptibility to S. pneumoniae was significantly increased at 6 days but not 3 days after an influenza infection. We depleted mice of neutrophils and found that neutrophils were important in the response to S. pneumoniae in mice infected with bacteria only or those infected with influenza for 3 days prior to a S. pneumoniae infection. However, at 6 days, neutrophil depletion did not alter the response to bacterial growth, indicating that neutrophil function was altered. We measured reactive oxygen species (ROS) generation and phagocytosis of S. pneumoniae by lung and bone marrow neutrophils isolated from mice infected with influenza for 3 or 6 days and compared these to neutrophils from either mice stimulated with LPS to induce neutrophil migration or from uninfected mice.