Abstract
The identification of biosignatures of aerosol exposure to pathogens has the potential to provide useful diagnostic information. In particular, markers of exposure to different types of respiratory pathogens may yield diverse sets of markers that can be used to differentiate exposure. We examine a mouse model of aerosol exposure to known Gram negative bacterial pathogens, Francisella tularensis novicida and Pseudomonas aeruginosa. Mice were subjected to either a pathogen or control exposure and bronchial alveolar lavage fluid (BALF) was collected at four and twenty four hours post exposure. Small protein and peptide markers within the BALF were detected by matrix assisted laser desorption/ionization (MALDI) mass spectrometry (MS) and analyzed using both exploratory and predictive data analysis methods; principle component analysis and degree of association. The markers detected were successfully used to accurately identify the four hour exposed samples from the control samples. This report demonstrates the potential for small protein and peptide marker profiles to identify aerosol exposure in a short post-exposure time frame.
Highlights
Developing molecular markers of infectious disease is a subject of intense interest
Bronchial Alveolar Lavage (BAL) Fluid Cell Measurements The bacterial cell load was assessed through direct culture in separate experiments
As seen in table 1, the number of colony forming units was measured to be one to four thousand for both the wild-type (Fn) and attenuated (Fn-ATT) F. novicida with significantly larger dose measured for the P. aeruginosa (Pa) exposure
Summary
Developing molecular markers of infectious disease is a subject of intense interest. Early detection of infection, prior to the onset of symptoms and pathology is the ultimate goal. The time scale for early detection is a few hours to days after infection before common symptoms of illness (e.g. fever, malaise, and congestion) appear [1]. This time scale precedes the mounting of an effective acquired immune response and is of particular interest for rapid detection of exposure. Aerosol exposure to infectious agents is a commonly discussed bioterrorism scenario because of the potential for affecting large numbers of people [1,2,3,4]. We focus on the tools to examine the early markers of host response to aerosol exposure in a mouse model of tularemia
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