Fungal-strain-dependent alterations in the time course and mortality of chronic murine pulmonary blastomycosis

Abstract

Intratracheal injection of 104 conidia of Blastomyces dermatitidis strain Mi-A into mice was shown in previous work to induce chronic pulmonary and disseminated infection with histopathologic features of chronic human blastomycosis. Furthermore, 10-fold variations in inoculum density produced marked changes in mean survival times (MSTs), i.e., 32 days at 106, 36 days at 105, 97 days at 104, and 172 days at 103. A second strain (Mi-B) failed to induce death in this model. To assess fungal-strain-dependent virulence, we extended these previous studies to 11 additional human isolates. Groups of male BALB/cByJ mice (6 to 8 weeks old) were injected intratracheally with 104 conidia from each of the 13 strains; the mice were weighed weekly and monitored for mortality, and their lungs were examined histopathologically. Infection rate and mortality were 100% in all groups except for the Mi-B inoculated mice. For strains Mi-B and Mi-A, MST and mortality curves were not significantly different from those observed in our previously reported experiments. Four different survival patterns were noted in infected mice. The shortest MSTs were produced by strains M2-E, M2-B, M2-K, M2-H, and M2-A (24, 26, 26, 27, and 31 days, respectively), and the longest MST was seen in animal groups inoculated with strains M2-J and M2-G (130 and 134 days, respectively). Strains M2-I, M2-F, and M2-D produced intermediate MSTs of 65, 79, and 80 days, respectively. The 107-day MST induced by Mi-A did not differ from strain M2-C-induced MST but differed significantly from the MST produced by the other strains. Pulmonary histopathology was similar in all animals dying with blastomycosis. The wide spectrum in survival times was not related to differences in clinical status of the patient from whom the isolate had been obtained, to fungal inoculum viability, or to individual mouse weight at inoculation. Strain-dependent virulence factors present in these fungal isolates alter the disease course in inbred mice in a fashion similar to that induced by 10-fold inoculum variation of strain Mi-A conidia. These 13 isolates of B. dermatitidis, 1 avirulent and 12 with differing levels of virulence, provide tools for future studies into the nature of fungal virulence determinants in chronic blastomycosis.

The Regulation of Pulmonary Immunity

“…Lung infections with two microorganisms, Mtb and Cryptococcus neoformans (Cne), are discussed in this section as examples of infections requiring intact CMI for resolution. Animal models of chronic lung infections with several other important pathogenic organisms have been studied, including Pneumocystis carinii (Walzer, 1984;Shel-lit0 et al, 1990;Harmsen and Stankiewicz, 1990;Boylan and Current, 1992), Histoplasma capsdatum (Baughman et al, 1986;Defaveri and Graybill, 1991;Fojtasek et al, 1993;Allendoerfer et al, 1993), Blastomyces dermitiditis (Morozumi et al, 1982;Moser et al, 1988;Frey et al, 1989;Williams et al, 1994), Paracoccidiodes braziliensis (Brummer et al, 1984;Defaveri et al, 1989), Coccidiodes immitis (Cox et al, 1988), Chlamydia trachomatis and psittaci (Williams et al, 1988), Rhodococcus equi (Kanaly et al, 1993), and Mycobacterium auiumintracellulare (Takashima and Collins, 1988). Although infection with Legionella pneumophila can cause an acute pneumonia in susceptible hosts, it is a facultative intracellular bacterium; CMI is thought to be necessary for resolution of the infection.…”

Successful treatment of chronic canine blastomycosis in a Labrador retriever with sterile histopathology

“…Pathogen factors such as low virulence of the infecting Blastomyces strain or a small dose of inoculum may also explain the slow progression of disease and low number of organisms. Variable strain‐dependent virulence resulting in altered disease course and survival times has been reported in mice with pulmonary blastomycosis (Moser and others 1988). Also seen in mice, smaller doses of inoculum resulted in slower disease progression and longer survival times (Williams and Moser 1987).…”