Early transcriptional response of Paracoccidioides brasiliensis upon internalization by murine macrophages

Insights into the pathobiology of Paracoccidioides brasiliensis from transcriptome analysis—advances and perspectives

“…Genes implicated in glucose and amino acid depletion (pfkA, phosphofructokinase; gapdh, glyceraldehyde-3-phosphate dehydrogenase; pgk, phosphoglycerate kinase; gpma, phosphoglycerate mutase; eno, enolase; metG, cystathionine b-lyase), cell wall metabolism (fks, a-glucan synthase), and oxidative stress (sod3, Cu,Zn superoxide dismutase and hsp60, 60 kDa heat shock protein) were differentially expressed by P. brasiliensis upon macrophage infection. The data showed a considerable degree of transcriptional plasticity by P. brasiliensis in response to the hostile environment of macrophages, which is expected to underlie its adaptability and consequent survival inside that cell [30].…”

“…In order to focus the research on the interaction of P. brasiliensis with the human host, 1,152 cDNA clones of interest were selected from the transcriptional database, based on previous findings of P. brasiliensis transcriptome [9], including putative virulence factors, general metabolism enzymes, heat shock proteins, cell wall synthetic enzymes and also some of unknown function. In addition, the protocol of RNA extraction from P. brasiliensis yeast cells internalized by murine macrophages, without any additional fungal in vitro growth was standardized [30]. They observed that early phagocytized P. brasiliensis also sense and respond to the phagosomal environment.…”

“…In response to the oxidative stress generated by the macrophage, the P. brasiliensis counter attacks inducing antioxidant gene such as sod3 [30]. In silico analysis showed that the deduced amino acid sequence of the P. brasiliensis sod3 homologue codes a putative membrane GPI-anchored Cu,Zn SOD [42], which would make it more directly accessible to host-derived superoxide anions and thus be more efficient at ROI detoxification.…”

“…brasiliensis has been shown to be refractory to classical genetic analysis. Recently, however, careful analyses have established that it has a genome of [26][27][28][29][30][31][32][33][34][35] Mb distributed in four or five chromosomes [3][4][5]. Ploidy is not consensual; some groups have proposed several isolates to be diploid [3,4], whereas other have used different techniques to propose that most isolates be either haploid or aneuploid [5].…”

“…Recently, the genes modulated in the hostpathogen interaction were evaluated trough the transcriptional response of P. brasiliensis when yeast cells were internalized into macrophage cells [30]. In addition, Bailão et al [31] also analyzed genes with differential expression when yeast cells were in contact with human blood and rescued from infected mice, to identify the genes required to the P. brasiliensis adaptation on the host interaction.…”