Respiratory infection of neonatal mice with an aerosol of Bordetella pertussis provides a reproducible system for the study of the host-pathogen interactions involved in respiratory infection and subsequent disease. Following infection with wild-type B. pertussis 18323, B. pertussis grows in the lungs of infected mice, concomitant with an increase in peripheral leukocyte count and decrease in weight, followed by death. Infection with wild-type B. pertussis 18323 results in neutrophil influx into the alveolar spaces of the lungs culminating in tracheo-bronchial pneumonia 19 days post-infection. Following aerosol infection with a transposon insertion mutant of 18323 deficient in the expression of pertussis toxin, this mutant persisted in the lungs of infected mice at lower levels than wild-type 18323 and did not cause leukocytosis, death or an inflammatory response. This data suggested that expression of pertussis toxin by B. pertussis is critical for high level persistence of this pathogen in the respiratory tract. In order to test this hypothesis, mice were infected with several different strains of B. pertussis in which the genes coding for pertussis toxin had been deleted. Little difference was observed between the levels of persistence of the toxin-negative strains, and their streptomycin-resistant parents. However, it was observed that the streptomycin-resistant parental strains colonized less well in comparison to the identical strains lacking the streptomycin resistance marker. Therefore, different antibiotic-resistance markers that do not interfere with the ability of B. pertussis to colonize the respiratory tract need to be used in the construction of these strains. Future studies with these new strains will analyze the role of particular virulence factors in establishing a successful infection and in the induction of inflammation.
NIH ExPorter
NIH ExPorter