there is no preclinical mouse model to investigate pulmonary Mycobacteroides abscessus (formerly Mycobacterium abscessus) infection in an immunocompetent mouse strain, especially in the context of antibiotic testing and regimen development. We developed a mouse model of pulmonary M. abscessus infection using the aerosolized route of infection that leads to an increase in bacterial burden postimplantation and develops pathology as a result. in this mouse model, treatment with corticosteroid allows for initial proliferation and sustained M. abscessus pulmonary infection and permits evaluation of efficacies of antibiotics. Administration of corticosteroids that permitted higher levels of bacterial burden in the lungs were more likely to have pathology. treatment of mice with antibiotics administered intranasally or subcutaneously significantly reduced lung M. abscessus burden. in addition to the reference strain, independent clinical isolates of M. abscessus also readily establish infection and proliferate in the lungs of mice in this model. In the setting of structural lung conditions such as cystic fibrosis, bronchiectasis, and COPD, Mycobacteroides abscessus (formerly Mycobacterium abscessus) can cause chronic pulmonary infection 1,2 that is often incurable and associated with rapid lung function decline 3-5. There is a current interest in developing new drugs and regimens to treat M. abscessus infection, as the cure rate with existing antibiotics is only 30-50% 6. While there have been many exciting demonstrations of in vitro potencies of antibiotics against M. abscessus 7-13 , it has also been established that potency observed in vitro for M. abscessus often does not translate to an equivalent clinical efficacy in the case of pulmonary infections 3. This highlights the need for a preclinical animal model to evaluate experimental antibiotics. A mammalian model that recapitulates aerosol infection leading to progressive M. abscessus burden and development of lung pathology as observed in human disease would facilitate preclinical studies of antibiotic efficacy and M. abscessus genetic determinants for virulence. In investigations of Mycobacterium tuberculosis (M. tuberculosis), several studies have demonstrated that aerosol infected C3HeB/FeJ mice closely mimic human pulmonary pathology 14-17. However, when infected with M. abscessus, these mice are able to clear the infection 18. Other immunocompetent mouse strains also clear the infection over time, although certain genetically manipulated immunocompromised strains were able to maintain bacterial burden 19-22. This is a compromise in favor of perpetuating the infection, but at a loss of immune cells and inflammatory markers normally observed in response to infection. Therefore, as mice are unable to mount an immune response, this precludes evaluation of critical aspects of host-pathogen interactions and pathology development that may impact efficacy of antibiotic treatments. We hypothesized that transient pharmacologically-induced immune suppression of immunoco...
STUDY OF REAL-TIME SPATIAL AND TEMPORAL BEHAVIOR OF BACTERIAL BIOFILMS USING 2D IMPEDANCE SPECTROSCOPYThe study of biofilms and their effect on disease treatment, prevention, and cures has been increasing in importance in recent years. Bacterial biofilms are colony formations developed by bacteria that allow them to anchor onto a surface and survive hostile environments. The formation of harmful bacteria biofilms on some surfaces can be troublesome, particularly in the case of medical implants.The continuing rise of antibiotic resistant bacteria over the past decade had escalated the need to study and understand biofilms. This thesis presents the design of a multi-channel impedance spectroscopy instrument to allow 2D spatial and temporal evaluation of biofilm growth. The custom-designed circuits allow measurement updates once per second on the entire set of impedance sensors. The distance between the neighboring sensors is 220 micrometers, allowing realtime observation of biofilm growth. The initial results show that the proposed 2D impedance spectroscopy tool provides the needed accuracy to predict the existence of bacteria biofilm at a given sensor location. The initial results were validated using optical images with fluorescent staining.
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