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Theses and Dissertations

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Browsing Theses and Dissertations by Subject "abscessus"

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    Comparative physiology of Mycobacterium abscessus in synthetic laboratory medium and cystic fibrosis sputum
    (Colorado State University. Libraries, 2019) Wiersma, Crystal J., author; Jackson, Mary, advisor; Borlee, Bradley, committee member; Jahn, Courtney, committee member
    Mycobacterium abscessus complex is a group of rapid-growing nontuberculous mycobacteria that are multidrug resistant and that cause chronic pulmonary infections in individuals with cystic fibrosis (CF) and other pre-disposing conditions. Research progress is challenged by the lack of laboratory models that mimic the lung environment, a nutritionally complex environment not well represented by current laboratory medium. In this study, the growth characteristics and gene expression profile of a diverse panel of M. abscessus isolates were characterized and compared when grown in 7H9 Middlebrook medium (a synthetic Mycobacterium laboratory culture medium); Synthetic Cystic Fibrosis Medium 2 (SCFM2), a medium which mimics the composition of CF sputum; and actual patient CF sputum. Tests were also performed measuring the antibiotic susceptibility and characterizing the cell envelope composition of the M. abscessus isolates in these media. Although the medium composition did not affect the antibiotic susceptibility or growth of the isolates, it caused changes in fatty acid and outer membrane lipid compositions which may account, at least in part, for observed differences in the subsequent infectivity of the isolates inside macrophages and epithelial cells. The gene expression profiles showed similar upregulation of pathways related to carbon metabolism for Mycobacterium abscessus grown in SCFM2 and grown in CF sputum while reaffirming the complexity of CF sputum and the many metabolic and structural adaptations that M. abscessus undergoes during growth in varied environments.
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    Understanding Mycobacterium abscessus pulmonary and disseminated disease
    (Colorado State University. Libraries, 2017) Layer, Emily L., author; Ordway, Diane, advisor; Orme, Ian, committee member; Chatterjee, Delphi, committee member; Kirby, Michael, committee member
    Mycobacterium abscessus is an emerging human pathogen which is difficult to treat and results in increased mortality. Moreover, the cause of increasing case rates and also the pathogenesis of M. abscessus are poorly understood. M. abscessus belongs to the family of nontuberculous mycobacteria (NTM) classified as members of the rapidly growing mycobacteria (RGM). These environmental pathogens are ubiquitous and found in shower heads, tap water, natural water sources, and soil. Humans contract pulmonary or disseminated infections with M. abscessus by breathing in the aerosolized bacteria or ingesting contaminated water. Immunocompromised individuals such as HIV or AIDS patients, are more susceptible to infection with M. abscessus as are those with cystic fibrosis, bronchiectasis, and individuals on tumor necrosis factor α (TNFα) inhibitors. Strangely, an increasing population of patients becoming infected with M. abscessus are immunocompetent, tall, slender, Caucasian, non-smoking women. To expand our understanding of M. abscessus pathogenesis we developed mouse models that maintain high levels of bacterial infection to study immune responses induced by clinical strains of M. abscessus. Our results support the hypothesis that this bacteria can only persist in our animal models that possess a deficiency in macrophages and T cell function. Clustered bacterial strains obtained from Cystic Fibrosis patients are more virulent than unclustered bacterial strains obtained from Cystic Fibrosis patients. Additionally, counts of viable mycobacterial colony forming units and histological analysis in (Severe Combined Immunodeficiency) SCID mice on a beige background infected with clustered versus unclustered M. abscessus strains which were isolated from Cystic Fibrosis patients also supported the increased virulence exhibited by the clustered strains. Lastly, we show that major human M. abscessus outbreak strains, when infecting IL-3, GM-CSF deficient mice on an IL-2, Rag2 deficient background (GM/Rag-dblKO mice), result in increased bacterial replication and organ pathology and impaired protective immunity against this pathogen.