Paracoccidioides brasiliensis 14-3-3 protein is important for virulence in a murine model

Abstract

The Paracoccidioides brasiliensis strain downregulated the expression of adhesin Pb14-3-3 (Pb14-3-3 aRNA) was evaluated in a murine model of paracoccidioidomycosis (PCM). Pb14-3-3 aRNA displays attenuated virulence and triggered the formation of fewer granulomas by lowering the fungal burden in the lungs. Additionally, the Pb14-3-3 aRNA showed more elongated yeast cells and less ability to induce pneumocytes apoptosis in vitro. Our results show that 14-3-3 is an important virulence factor in P. brasiliensis-induced pulmonary infection.

Prospecting Biomarkers for Diagnostic and Therapeutic Approaches in Pythiosis

“…The downregulation of Pb14-3-3 leads to morphological modifications, such as more elongated cells, an impairment in dimor-phism, decreased interaction with pneumocytes, and reduced bud number [101]. Still, in P. brasiliensis, Marcos et al [102] observed that the downregulation of the 14-3-3 protein alters the pathogen's ability to cause host cell apoptosis, which may be due to a consequence of the decreased secretion of Pb14-3-3 or the loss of putative adherence mediated by 14-3-3. In Pythium insidiosum, this protein may be related to the pathogen's virulence favoring the adhesion process, as mentioned in the literature.…”

“…These antigens have already been demonstrated to be crucial in the pathogenesis and virulence of several fungi, such as Histoplasma capsulatum [63,64], Paracoccidioides spp. [61,65,75,76,80,100,102], Aspergillus fumigatus [84], Saccharomyces cerevisiae [60,82,89], Cryptococcus neoformans [79,90], and Candida albicans [83]; as well as in studies involving the development of vaccines for Candida albicans [77,78] and Paracoccidioides spp. [103].…”

In Vitro and In Vivo Effect of Peptides Derived from 14-3-3 Paracoccidioides spp. Protein

“…The 14-3-3 protein is an important virulence factor of Paracoccidioides spp. acting as an essential adhesin [17][18][19]. Therefore, we aimed to determine candidates of immunogenic peptides from this protein and evaluate their biological activity and immunogenic potential in vitro and in vivo.…”

“…In addition, the S. cerevisiae strain showed increased expression of genes in the ergosterol pathway, the target for azoles [17]. Marcos et al [18,19], using a 14-3-3-silenced strain of P. brasiliensis, demonstrated that in vitro 14-3-3 is important to the interaction with pneumocytes, and in vivo, showed less virulence in both G. mellonella and murine models, causing low granuloma and fungal burden in the last model. In this way, 14-3-3 protein is considered an important virulence factor of Paracoccidioides spp.…”

One Century of Study: What We Learned about Paracoccidioides and How This Pathogen Contributed to Advances in Antifungal Therapy

“…The scientific community looks forward to seeing the CRISPR/CAS9 system, which is widely used for functional study of genes in fungal kingdom members, being applied to Paracoccidioides shortly. Even with this delay in the development of appropriate molecular tools compared to other human pathogenic fungi, several studies have been published in the past few years, using the gene expression modulation approach described by Almeida et al [51][52][53][54][55][56][57][58][59][60].…”