Transferrin independent serum inhibition of Blastomyces dermatitidis

Human serum has been reported to inhibit the growth of several fungal pathogens. Serum inhibitory activity has predominantly been associated with transferrin-mediated iron binding. We found that serum from several animal species (human, dog, mouse and fetal bovine) inhibited the growth of the dimorphic fungal pathogen, Blastomyces dermatitidisin vitro. In initial studies, we found no correlation between the total iron-binding capacity of various sera and their inhibitory activity against B. dermatitidis yeast. In addition, we were unable to abrogate the inhibitory activity of human serum against B. dermatitidis yeast by the addition of ferric chloride (10-200 microM). We found that apo-transferrin had little or no inhibitory activity against B. dermatitidis yeast. Furthermore, serum from hypotransferrinemic mice (hpx/hpx) had inhibitory activity against B. dermatitidis yeast that was equivalent to that of normal mouse serum. These findings are consistent with our initial findings and suggest that serum inhibitory activity against B. dermatitidis yeast is transferrin independent. Although high concentrations (3.5-5 mg/ml) of lactoferrin did have inhibitory activity against B. dermatitidis yeast, these concentrations were orders of magnitude greater than those found in serum under normal physiological conditions, suggesting that lactoferrin was not likely to contribute to serum inhibitory activity against B. dermatitidis yeast. Our findings suggest that host iron-binding proteins may be relatively ineffective in innate host defense against infection with B. dermatitidis yeast.