Memoria CD.indd - ISHAM

certain antifungal drugs. The effect of melanin on microbial susceptibility to drugs and host defensesmay be an important consideration in the selection and development of antimicrobial therapy. Workconducted by different groups has characterized melanogenesis in the important dimorphic fungalpathogens Paracoccidioides brasiliensis, Histoplasma capsulatum, Sporothrix schenckii, Blastomycesdermatitidis, Coccidioides posadassi and more recently in Candida albicans. These findings andtheir possible clinical impact will be discussed and reviewed in this presentation with special focuson recent developments in P. brasiliensis, the etiological agent of paracoccidioidomycosis (PCM).Both conidia and yeast cells of this thermally dimorphic fungal pathogen produce melanin or melanin-likecompounds in vitro and in vivo. Our results demonstrate that P. brasiliensis synthesizes andpolymerizes melanin during infection and generates antibodies, principally IgG but not IgM, againstconidia and yeast melanins, as detected in sera and BALs such as reported previously for other fungi.The mouse anti-P.brasiliensis melanin MAbs obtained by our group and the significance of antibodyresponse in vivo will be useful in the study of P. brasiliensis melanization, particularly in regardsto passive immunization for prolonged survival of infected mice and/or modulation of the immuneresponse against this fungal infection. Another important and recent contribution (da Silva MB et al,2006) indicates that P. brasiliensis production of melanin may contribute to virulence by reducing theuptake of yeast cells by peritoneal and alveolar macrophages. This would enhance the resistanceof fungal cells to attack by the immune effector system. Melanized cells were observed to be lesssusceptible to potent antifungal drugs, in particular amphotericin B, ketoconazole, fluconazole, itraconazoleand sulfamethoxazole. We are currently investigating potential role(s) of melanogenesisin the pathogenesis of P. brasiliensis infection.63