Beyond melanin: Proteomics reveals virulence-related proteins in paracoccidioides brasiliensis and paracoccidioides lutzii yeast cells grown in the presence of l-dihydroxyphenylalanine

Rodrigo Almeida-Paes, Marcos Abreu Almeida, Lilian Cristiane Baeza, Leticia Andrade Mendes Marmello, Monique Ramos de Oliveira Trugilho, Joshua Daniel Nosanchuk, Celia Maria de Almeida Soares, Richard Hemmi Valente, Rosely Maria Zancopé-Oliveira

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number328
Pages (from-to)1-18
Number of pages18
JournalJournal of Fungi
Volume6
Issue number4
DOIs
StatePublished - Dec 2020

Keywords

  • L-dihydroxyphenylalanine
  • Melanin
  • Metabolism
  • Paracoccidioides
  • Proteomics
  • Virulence

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Plant Science
  • Microbiology (medical)

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