Project description:Examination and comparison of the transcriptional profile of bone marrow derived dendritic cells (BMDCs) in response to infection by the fungus Paracoccidioides brasiliensis in resistant/susceptible mice
Project description:Paracoccidioides brasiliensis is a thermodimorphic fungus associated with paracoccidioidomycosis (PCM), a prevalent systemic mycosis in South America. In humans, infection starts by inhalation of fungal propagules, which reach the pulmonary epithelium and transform into the yeast parasitic form. Thus, the mycelium-to-yeast transition is of particular interest because conversion to yeast is essential for infection. We have used a P. brasiliensis biochip, carrying sequences of 4,692 genes from this fungus to monitor gene expression at several time points of the mycelium-to-yeast morphological shift (from 5 to 120 h). Keywords: Time Course
Project description:Phenothiazines are antipsychotic drugs used in the treatment of schizophrenia, which have been shown to present antimicrobial activity (in vitro and in vivo) against a great variety of pathogenic microorganisms, including bacteria, parasites (protozoa and helmints) and fungi. In this study, we used competitive microarray hybridization to evaluate the effects of increasing concentrations of the piperidinic phenothiazine derivative thioridazine (TR) on the transcriptome of Paracoccidioides brasiliensis, the causative agent of paracoccidioidomycosis (PCM) - the most common systemic mycosis in Latin America. These analyses showed that the presence of TR affected expression of more than 1,800 genes from this fungus, including genes related to cellular processes such as cell wall metabolism and drug resistance.
Project description:Species of the genus Paracoccidioides cause a systemic infection in human patients. Yeast cells of Paracoccidioides spp. produce melanin in the presence of L-dihydroxyphenylalanine and during infection, which may impact the pathogen survival into the host. To better understand the metabolic changes that occur in melanized Paracoccidioides spp. cells, a proteomic approach was performed to compare melanized and non-melanized Paracoccidioides brasiliensis and Paracoccidioides lutzii yeast cells. Melanization was conducted using L-dihydroxyphenylalanine as a precursor and quantitative proteomics was performed using reversed-phase chromatography coupled to high resolution mass spectrometry. When comparing melanized versus non-melanized cells, 999 and 577 differentially abundant proteins were identified for P. brasiliensis and P. lutzii, respectively. Functional enrichment and comparative analysis revealed 30 abundant biological processes in melanized P. brasiliensis and 18 in P. lutzii, while non-melanized cells from these species had 21 and 25 differentially abundant processes, respectively. Melanized cells presented abundance of other virulence-associated proteins, such as phospholipase, proteases, superoxide dismutase, heat-shock proteins, as well as proteins related to cell-wall remodeling and vesicular transport. The results suggest that L-dihydroxyphenilalanine increases virulence of Paracoccidioides spp. through a complex mechanism involving not only melanin, but other virulence factors as well.