Angela Restrepo

Histoplasma capsulatum synthesizes melanin-like pigments in vitro and during mammalian infection.

ABSTRACT Melanin is made by several important pathogenic fungi and has been implicated in the pathogenesis of a number of fungal infections. This study investigated whether the thermally dimorphic fungal pathogen Histoplasma capsulatum var. capsulatum produced melanin or melanin-like compounds in vitro and during infection. Growth of H. capsulatum mycelia in chemically defined minimal medium produced pigmented conidia. Growth of H. capsulatum yeast in chemically defined minimal medium with l-3,4-dihydroxyphenylalanine (DOPA) or (-)-epinephrine produced pigmented cells. Treatment of the pigmented cells with proteolytic enzymes, denaturant, and hot concentrated acid yielded dark particles that were similar in size and shape to their respective propagules. Melanin-binding monoclonal antibodies (MAb) labeled pigmented conidia, yeast, and the isolated particles as determined by immunofluorescence microscopy. Electron spin resonance spectroscopy revealed that pigmented yeast cells and particles derived from pigmented cells were stable free radicals consistent with their identification as melanins. Tissues from mice infected with H. capsulatum and from biopsy specimens from a patient with histoplasmosis contained fungal cells that were labeled by melanin-binding MAb. Digestion of infected mouse tissues yielded dark particles that reacted with the melanin-binding MAb and were similar in appearance to H. capsulatum yeast cells. Additionally, sera from infected mice contained antibodies that bound melanin particles. Phenoloxidase activity capable of synthesizing melanin from L-DOPA was detected in cytoplasmic yeast cell extracts. These findings indicate that H. capsulatum conidia and yeast can produce melanin or melanin-like compounds in vitro and that yeast cells can synthesize pigment in vivo. Since melanin is an important virulence factor in other pathogenic fungi, this pigment may have a similar role to play in the pathogenesis of histoplasmosis.

Pulmonary Paracoccidioidomycosis: Clinical, Immunological and Histopathological Aspects

The systemic endemic mycoses are a group of microbial pathologies affecting primarily the lower respiratory tract, often overlooked in the evaluation of community-acquired pneumonia. They form a heterogeneous group caused by dimorphic fungi that share similar characteristics. All of them have the respiratory tract as the portal of entry and from the lungs they may disseminate to the mucous membranes, the skin, and many other organs. Nonetheless, each fungal disease has specific characteristics concerning its clinical course, diagnosis, and management. Interestingly, specific geographical areas of the world have been associated with acquisition of these mycoses. The diagnosis may be difficult and delayed owing to the varied manifestations and the multitude of differential diagnoses (Bonifaz et al., 2011; Hsu et al., 2010). The major endemic systemic mycoses include histoplasmosis, coccidioidomycosis, blastomycosis, paracoccidioidomycosis (PCM), and penicilliosis. All of them can cause disease in both immunocompetent and immunocompromised hosts, in particular, AIDS and organ transplantation patients, and more recently recipients of biological therapies, such as TNF inhibitors or antagonists. These mycoses have similar clinical and radiologic presentations but require different treatments. Furthermore, when they have spread to the lymph nodes or skin, they may mimic other pathologies such as leishmaniasis, lymphoma, and syphilis, among others (Bonifaz et al., 2011).