Human Pathogenic Fungi
Invasive fungal diseases pose a serious and growing health problem and are a major cause of death worldwide. Fungal pathogens have been relatively neglected as targets for basic research and consequently there is a pressing need for new prophylactic therapeutic measures for treating these diseases. With this objective in mind, molecular studies of fungal pathogens, such as Candida albicans, are in progress. However, in many developing countries other fungal pathogens predominate but receive less scientific attention. One such fungal pathogen is Paracoccidioides brasiliensis, the aetiological agent of paracoccidioidomycosis (PCM), which is by far the most prevalent human systemic mycosis in Latin America, with an estimated 10 million infected individuals in the area of endemicity. Infection can give rise to either an asymptomatic condition or to active disease and initially causes pulmonary lesions in the lungs but can subsequently disseminate to other organs and tissues. Regardless of the organ involved, paracoccidioidomycosis usually heals by fibrosis, with the formation of fibrotic sequelae, which can permanently interfere with the well-being of the patient.
P. brasiliensis is a dimorphic fungus that undergoes a complex transformation in vivo, with mycelia in the environment producing conidia, which probably act as infectious propagules upon inhalation into the lungs, where they transform to the pathogenic yeast form. The pathogenicity of the fungus is intimately linked to this morphological transition since strains that are unable to transform into the yeast form are avirulent. Furthermore, there is a strong gender bias towards infection of males, which is probably attributable to the fact that mammalian oestrogens inhibit the morphological transition. As a consequence, a viable treatment strategy might well involve the development of drugs that prevent this change in morphology. Our aim is to identify and characterize genes controlling this morphological change as potential drug targets.