Mouse model of pulmonary blastomycosis: utility, simplicity, and quantitative parameters

Abstract

A murine model of pulmonary mycotic disease using Blastomyces dermatitidis is defined quantitatively. Intranasal inoculation with yeasts avoids delays in growing microconidia and can be performed with routine precautions without sophisticated biohazard facilities. The particles rapidly reach the bronchioles and alveoli, producing a progressive focal pneumonia, studied histologically. In vitro growth conditions are defined to titer inocula reproducibly with visual methods. Median survival can be titrated with the challenge inocula. Although initial postchallenge lung cultures are not always positive, replication eventually proceeds, at a rate defined for various challenge sizes, to a ceiling of 10(7) to 10(8) colony-forming units per g of tissue incompatible with life. Lung weight correlates closely with colony-forming units per g above a threshold. Lethality correlates with initial body weight and with age. During the course of infection, weight is an accurate predictor of mortality. Extrapulmonary dissemination occurs as a premortem event in protracted infections. A wide variation in fungal strain virulence is documented. Quantification of these features of the model makes it useful for study of host response or therapeutic intervention, because efficacy can be related to stage of disease and parasitic burden.