Predicting copper-, iron-, and zinc-binding proteins in pathogenic species of the Paracoccidioides genus

Abstract

Approximately one-third of all proteins have been estimated to contain at least one metal cofactor, and these proteins are referred to as metalloproteins. These represent one of the most diverse classes of proteins, containing metal ions that bind to specific sites to perform catalytic, regulatory and structural functions. Bioinformatic tools have been developed to predict metalloproteins encoded by an organism based only on its genome sequence. Its function and the type of metal binder can also be predicted via a bioinformatics approach. Paracoccidioides complex includes termodimorphic pathogenic fungi that are found as saprobic mycelia in the environment and as yeast, the parasitic form, in host tissues. They are the etiologic agents of Paracoccidioidomycosis, a prevalent systemic mycosis in Latin America. Many metalloproteins are important for the virulence of several pathogenic microorganisms. Accordingly, the present work aimed to predict the copper, iron and zinc proteins encoded by the genomes of three phylogenetic species of Paracoccidioides (Pb01, Pb03, and Pb18). The metalloproteins were identified using bioinformatics approaches based on structure, annotation and domains. Cu-, Fe-, and Zn-binding proteins represent 7% of the total proteins encoded by Paracoccidioides spp. genomes. Zinc proteins were the most abundant metalloproteins, representing 5.7% of the fungus proteome, whereas copper and iron proteins represent 0.3 and 1.2%, respectively. Functional classification revealed that metalloproteins are related to many cellular processes. Furthermore, it was observed that many of these metalloproteins serve as virulence factors in the biology of the fungus. Thus, it is concluded that the Cu, Fe, and Zn metalloproteomes of the Paracoccidioides spp. are of the utmost importance for the biology and virulence of these particular human pathogens.

Characterization of the Paracoccidioides Hypoxia Response Reveals New Insights into Pathogenesis Mechanisms of This Important Human Pathogenic Fungus

“…fumigatus SREBP is a key positive regulator of iron homeostasis, particularly related to iron acquisition, which is essential for adaptation to hypoxia and low iron microenvironments [ 95 ]. Iron homeostasis has been characterized in Paracoccidioides [ 11 , 12 , 96 – 98 ] and the elucidation of additional molecules involved in this process can be relevant in the understanding of fungus pathogenesis. In this sense, our purpose was firstly attempted to screen PbsrbA reconstituted strain susceptibility to antifungals drugs using ranges of azoles concentrations [ 37 ] ( Fig 8 ).…”

Paracoccidioides spp. ferrous and ferric iron assimilation pathways

“…The predicted proteins encoded by the transcripts identified through RNAseq strategy were also classified as copper−, iron−, and zinc-binding proteins from Paracoccidioides genome as previously described (Tristão et al, 2015 ). Briefly, metalloproteins were identified by using the RDGB tool (Andreini et al, 2011 ) with default options.…”

New insights into a complex fungal pathogen: the case of Paracoccidioides spp.

“…Several metalloproteins, such as Cu‐, Fe‐ and Zn‐binding proteins, have been identified using bioinformatic tools, representing 7% of the total proteins encoded by the genome of Paracoccidioides . Zinc proteins are the most abundant, representing 5.7% of the fungus proteome, with copper and iron proteins accounting for 0.3% and 1.2%, respectively (Tristão et al ., ).…”

“…Other virulence determinants include metalloproteinases, phospholipases, an alternative oxidase (AOX; an enzyme involved in intracellular redox balancing), p27 and heat‐shock proteins (Tristão et al ., ; Soares et al ., ; Ruiz et al ., ; Tamayo et al ., ; Torres e t al ., ). In addition, P .…”