title: Differentiation of gram-negative bacterial aerosol exposure using detected markers in bronchial-alveolar lavage fluid.
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.
authors.affiliation: Chemical and Biological Signature Sciences, Pacific Northwest National Laboratory, Richland, Washington, United States of America. David.Wunschel@pnl.gov
authors.forename: David
authors.initials: D
authors.lastname: Wunschel
authors.forename: Bobbie-Jo
authors.initials: BJ
authors.lastname: Webb-Robertson
authors.forename: Charles W
authors.initials: CW
authors.lastname: Frevert
authors.forename: Shawn
authors.initials: S
authors.lastname: Skerrett
authors.forename: Nat
authors.initials: N
authors.lastname: Beagley
authors.forename: Alan
authors.initials: A
authors.lastname: Willse
authors.forename: Heather
authors.initials: H
authors.lastname: Colburn
authors.forename: Kathryn
authors.initials: K
authors.lastname: Antolick
mesh_terms: D000336:Aerosols; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology*; D005260:Female; D005604:Francisella tularensis / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000378:metabolism*; D008168:Lung / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D025341:Principal Component Analysis; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014774:Virulence
chemical_list: D000336:Aerosols; D015415:Biomarkers