Anders Omsland, National Institutes of Health, Hamilton, MT, Katrina Miranda, University of Arizona, Tucson, AZ, Jessica A. Edwards, Arizona Health Sciences Center, Tucson, AZ, and Scott Boitano, Arizona Health Sciences Center, Tucson, AZ.
To successfully colonize the conducting airway of healthy mammalian hosts, members of the Bordetella genus of primary colonizing respiratory pathogens have to overcome extensive innate immune mechanisms of the airway epithelium. This innate immunity includes epithelial-derived antimicrobials present in airway surface liquid, where Bordetella establishes colonization. To better understand early events of bacterial colonization of the host airway, we have developed assays to test the ability of naturally occurring airway redox active species to function as bacteriostatic or bactericidal agents against Bordetella. Within their predicted physiological concentrations, nitric oxide (NO), superoxide (O2-) and hydrogen peroxide (H2O2) all displayed a dose-dependent activity against B. bronchiseptica. Bacterial susceptibility to prototypical redox active species was significantly increased when a second redox active species at sub-microbicidal concentration was introduced. Direct comparisons of B. bronchiseptica colony morphology following a lethal dose of 50% (LD50) redox challenge of NO and H2O2 suggested increased bacteriostatic activity of NO and increased bactericidal activity of H2O2. Further understanding of the Bordetella responses to physiologically relevant levels of host derived RNS and ROS will aid in defining events that result in pathogen clearance versus those resulting in colonization and disease.
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