Iron is an essential nutrient for all organisms. For pathogenic fungi, iron is essential for the success of infection. Thus, these organisms have developed high affinity iron uptake mechanisms to deal with metal deprivation imposed by the host. Siderophore production is one of the mechanisms that fungal pathogens employ for iron acquisition. Paracoccidioides spp. present orthologous genes encoding the enzymes necessary for the biosynthesis of hydroxamates, and plasma membrane proteins related to the transport of these molecules. All these genes are induced in iron deprivation. In addition, it has been observed that Paracoccidioides spp. are able to use siderophores to scavenge iron. Here we observed that addition of the xenosiderophore ferrioxamine B FOB) to P. brasiliensis culture medium results in repression (at RNA and protein levels) of the SidA, the first enzyme of the siderophore biosynthesis pathway. Furthermore, SidA activity was reduced in the presence of FOB, suggesting that P. brasiliensis blocks siderophores biosynthesis and can explore siderophores in the environment to scavenge iron. In order to support the importance of siderophores on Paracoccidioides sp. life and infection cycle, silenced mutants for the sidA gene were obtained by antisense RNA technology. The obtained AsSidA strains displayed decreased siderophore biosynthesis in iron deprivation conditions and reduced virulence to an invertebrate model.

Aim:During infection development in the host, Paracoccidioides spp. faces the deprivation of micronutrients, a mechanism called nutritional immunity. This condition induces the remodeling of proteins present in different metabolic pathways. Therefore, we attempted to identify membrane proteins and their regulation by zinc in Paracoccidioides lutzii.Materials & methods:Membranes enriched fraction of yeast cells of P. lutzii were isolated, purified and identified by 2D LC–MS/MS detection and database search.Results & conclusion:Zinc deprivation suppressed the expression of membrane proteins such as glycoproteins, those involved in cell wall synthesis and those related to oxidative phosphorylation. This is the first study describing membrane proteins and the effect of zinc deficiency in their regulation in one member of the genus Paracoccidioides.

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Introdução: Os exossomos são pequenas vesículas com diâmetro que varia entre 40 e 100 nm, produzidas pelo sistema endocítico de diversos tipos celulares. O interesse recente nos exosssomos é atribuído ao seu papel na disseminação de organismos patogênicos, bem como na sua função em promover e regular a resposta imune. Destaca-se ainda o promissor uso dos exossomos como biomarcadores de doenças e como ferramentas terapêuticas. Além de mediarem a comunicação intercelular, os exossomos também estão envolvidos em enfermidades como câncer e doenças degenerativas. Objetivo: Levantar novas abordagens relacionadas aos exosossomos, sua formação, função e sua relevância para o uso de novas técnicas diagnósticas e terapêuticas, e durante a interação parasito-hospedeiro. Metodologia: Este é um estudo de revisão bibliográfica desenvolvido através de levantamento na literatura sobre o tema abordado. Resultados e discussão: Os exossomos tem sido atribuído a diferentes funções biológicas, entre elas estão a influência no sistema imune, transferência de receptores de uma célula para outra, assim como a entrega de mRNAs, miRNAs e proteínas específicas da célula de origem para o citoplasma da célula recipiente. Os exossomos facilitam também o transporte e disseminação de patógenos. Sua análise tem sido descrita em abordagens diagnósticas e terapêuticas. Conclusão: Componentes específicos dos exossomos tem mostrado serem uma ferramenta não invasiva no diagnóstico de doenças como câncer, além disso desempenham importantes papéis durante a interação parasito-hospedeiro.Palavras chave: exossomos, biomarcadores, terapias, patógenos, comunicação celular.

Fungal infections increased substantially in the last years, becoming a relevant public health problem. Many of these infections account for high rates of morbidity and mortality. The emergence of resistant fungal clinical isolates have also motivate studies to find new antifungal therapies. Candida albicans is an oportunistic pathogen and affects a great number of immunocompromised patients worldwide. The marine ecosystem has been considered a rich source of bioactive metabolites due to the complexity and originality of its structures. Proteins and peptides from marine organisms have been shown to have antiviral, anti-inflammatory, antimalarial, anticancer, antimicrobial and antifungal properties. Arenicins are antimicrobial peptides isolated from the marine lugworm Arenicola marina with 21 amino acid residues in a β-hairpin structure. Dihydrofolate reductase, exo-b-(1,3)-glucanase and sterol 14α-demethylase are essential C. albincas enzymes that take part in DNA, cell wall and membrane metabolism, respectively. The present study evaluates the interaction of arenicin with important enzymes of C. albicans related to cell wall, ergosterol and DNA metabolism in order to elucidate possible molecular targets. We showed through an in silico approach, that a single compound from a marine worm (A. marina), can bind to three C. albicans essential proteins. The interaction occurs in regions inside the active site or at least near, with amino acid residues evaluated as hot spots. Arenicin is a new promising antifugal drug. The next step is to investigate protein-protein interactions performed by DHFR, EBG and CYP51 and assess whether arenicin is able to disrupt essential interaction or not.

Paracoccidioides is a genus of thermodimorphic fungi that causes paracoccidioidomycosis. When in the host, the fungus undergoes several challenges, including iron deprivation imposed by nutritional immunity. In response to the iron deprivation triggered by the host, the fungus responds in a ternary manner using mechanisms of high affinity and specificity for the uptake of Fe, namely non-classical reductive iron uptake pathway, uptake of host iron proteins, and biosynthesis and uptake of siderophores. This triple response resembles the rhythmic structure of a waltz, which features three beats per compass. Using this connotation, we have constructed this review summarizing relevant findings in this area of study and pointing out new discoveries and perspectives that may contribute to the expansion of this “little iron waltz”.

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