Effect of Nitrosative Stress on the S-Nitroso-Proteome of Paracoccidioides brasiliensis

Navarro, Marina Valente; Chaves, Alison Felipe Alencar; Castilho, Daniele Gonçalves; Casula, Isis; Calado, J; Conceição, Palloma Mendes; Iwai, Leo Kei; Castro, Beatriz F de; Batista, Wagner L.

doi:10.3389/fmicb.2020.01184

Cited by 7 publications

(8 citation statements)

References 95 publications

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“…The results of the proteomic approach used in this study revealed that, besides the well-established function of melanization promotion [ 13 , 14 ], L-DOPA also induces the expression of several other molecules related to fungal virulence in Paracoccidioides spp. Similar behavior was observed for the Pb 18 strain treated with low doses of nitric oxide [ 54 ]. We found that Pb 18 presented more virulence-related proteins, with higher abundance than Pb 01, which can be related to the higher virulence of this strain in experimental mice models of paracoccidioido-mycosis [ 8 ].…”

Section: Discussionsupporting

confidence: 78%

Beyond Melanin: Proteomics Reveals Virulence-Related Proteins in Paracoccidioides brasiliensis and Paracoccidioides lutzii Yeast Cells Grown in the Presence of L-Dihydroxyphenylalanine

Almeida‐Paes¹,

Almeida²,

Baeza

et al. 2020

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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’s survival in 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 induced using L-dihydroxyphenylalanine as a precursor, and quantitative proteomics were performed using reversed-phase nano-chromatography coupled to high-resolution mass spectrometry. When comparing melanized versus non-melanized cells, 1006 and 582 differentially abundant/detected proteins were identified for P. brasiliensis and P. lutzii, respectively. Functional enrichment and comparative analysis revealed 30 important KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways in melanized P. brasiliensis and 18 in P. lutzii, while differentially abundant proteins from non-melanized cells from these species were involved in 21 and 25 enriched pathways, respectively. Melanized cells presented an abundance of additional virulence-associated proteins, such as phospholipase, proteases, superoxide dis-mutases, heat-shock proteins, adhesins, and proteins related to vesicular transport. The results suggest that L-dihydroxyphenylalanine increases the virulence of Paracoccidioides spp. through complex mechanisms involving not only melanin but other virulence factors as well.

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Section: Discussionsupporting

confidence: 78%

Beyond Melanin: Proteomics Reveals Virulence-Related Proteins in Paracoccidioides brasiliensis and Paracoccidioides lutzii Yeast Cells Grown in the Presence of L-Dihydroxyphenylalanine

Almeida‐Paes¹,

Almeida²,

Baeza

et al. 2020

JoF

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“…Molecular chaperones, usually known as heat shock proteins, are a diverse family of proteins that are upregulated under conditions of stress and operate to protect proteins from irreversible aggregation during synthesis and in times of cellular stress [ 147 , 148 ]. These molecular chaperones have been demonstrated to be modulated during the nitrosative stress in P. brasiliensis , suggesting that they play essential roles in fungal virulence [ 149 ]. Remarkably, the HSP60 protein, have been primarily explored in fungal cells and recognized to be crucial for cell growth [ 150 ], survival in the host, morphogenesis [ 151 , 152 ], germination, and conidiation [ 153 ].…”

Section: Discussionmentioning

confidence: 99%

Immunoproteomic Analysis Reveals Novel Candidate Antigens for the Diagnosis of Paracoccidioidomycosis Due to Paracoccidioides lutzii

Rodrigues

Kubitschek-Barreira

Pinheiro

et al. 2020

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Paracoccidioidomycosis (PCM) is a life-threatening systemic infection caused by the fungal pathogen Paracoccidioides brasiliensis and related species. Whole-genome sequencing and stage-specific proteomic analysis of Paracoccidioides offer the opportunity to profile humoral immune responses against P. lutzii and P. brasiliensis s. str. infection using innovative screening approaches. Here, an immunoproteomic approach was used to identify PCM-associated antigens that elicit immune responses by combining 2-D electrophoresis of P. lutzii and P. brasiliensis proteomes, immunological detection using a gold-standard serum, and mass spectrometry analysis. A total of 16 and 25 highly immunoreactive proteins were identified in P. lutzii and P. brasiliensis, respectively, and 29 were shown to be the novel antigens for Paracoccidioides species, including seven uncharacterized proteins. Among the panel of proteins identified, most are involved in metabolic pathways, carbon metabolism, and biosynthesis of secondary metabolites in both immunoproteomes. Remarkably, six isoforms of the surface-associated enolase in the range of 54 kDa were identified as the major antigens in human PCM due to P. lutzii. These novel immunoproteomes of Paracoccidioides will be employed to develop a sensitive and affordable point-of-care diagnostic assay and an effective vaccine to identify infected hosts and prevent infection and development of human PCM. These findings provide a unique opportunity for the refinement of diagnostic tools of this important neglected systemic mycosis, which is usually associated with poverty.

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“…Recently, a study detected S-nitrosylated proteins after submitting P. brasiliensis to low and high concentrations of NO. Several proteins involved in the cellular cycle and growth were identified in P. brasiliensis treated with low NO concentrations [144]. On the other hand, at high NO levels, S-nitrosylated proteins involved in the cell wall integrity (CWI) pathway and amino acid and folic acid metabolism were identified, which may represent molecular targets for fungal disease therapy.…”

Section: Extracellular Vesicles (Evs)mentioning

confidence: 99%

Updates in Paracoccidioides Biology and Genetic Advances in Fungus Manipulation

Chaves

Navarro

Barros

et al. 2021

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The dimorphic fungi of the Paracoccidioides genus are the causative agents of paracoccidioidomycosis (PCM). This disease is endemic in Latin America and primarily affects workers in rural areas. PCM is considered a neglected disease, despite being a disabling disease that has a notable impact on the public health system. Paracoccidioides spp. are thermally dimorphic fungi that present infective mycelia at 25 °C and differentiate into pathogenic yeast forms at 37 °C. This transition involves a series of morphological, structural, and metabolic changes which are essential for their survival inside hosts. As a pathogen, the fungus is subjected to several varieties of stress conditions, including the host immune response, which involves the production of reactive nitrogen and oxygen species, thermal stress due to temperature changes during the transition, pH alterations within phagolysosomes, and hypoxia inside granulomas. Over the years, studies focusing on understanding the establishment and development of PCM have been conducted with several limitations due to the low effectiveness of strategies for the genetic manipulation of Paracoccidioides spp. This review describes the most relevant biological features of Paracoccidioides spp., including aspects of the phylogeny, ecology, stress response, infection, and evasion mechanisms of the fungus. We also discuss the genetic aspects and difficulties of fungal manipulation, and, finally, describe the advances in molecular biology that may be employed in molecular research on this fungus in the future.

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Effect of Nitrosative Stress on the S-Nitroso-Proteome of Paracoccidioides brasiliensis

Cited by 7 publications

References 95 publications

Beyond Melanin: Proteomics Reveals Virulence-Related Proteins in Paracoccidioides brasiliensis and Paracoccidioides lutzii Yeast Cells Grown in the Presence of L-Dihydroxyphenylalanine

Beyond Melanin: Proteomics Reveals Virulence-Related Proteins in Paracoccidioides brasiliensis and Paracoccidioides lutzii Yeast Cells Grown in the Presence of L-Dihydroxyphenylalanine

Immunoproteomic Analysis Reveals Novel Candidate Antigens for the Diagnosis of Paracoccidioidomycosis Due to Paracoccidioides lutzii

Updates in Paracoccidioides Biology and Genetic Advances in Fungus Manipulation

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