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Iron Deprivation Modulates the Exoproteome in Paracoccidioides brasiliensis
Aparecido Ferreira de Souza1, Laurine Lacerda Pigosso1, Lana O'Hara Souza Silva1
1Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, ICB II, Campus II, Universidade Federal de Goiás, Goiânia, Brazil.
Abstract:
Fungi of the Paracoccidioides genus are the etiological agents of the systemic mycosis paracoccidioidomycosis and, when in the host, they find a challenging environment that is scarce in nutrients and micronutrients, such as Fe, which is indispensable for the survival of the pathogen. Previous studies have shown that fungi of this genus, in response to Fe deprivation, are able to synthesize and capture siderophores (Fe3+ chelators), use Fe-containing host proteins as a source of the metal, and use a non-canonical reductive pathway for Fe3+ assimilation. Despite all of these findings, there are still gaps that need to be filled in the pathogen response to metal deprivation. To contribute to the knowledge related to this subject, we obtained the exoproteome of Paracoccidioides brasiliensis (Pb18) undergoing Fe deprivation and by nanoUPLC-MSE. One hundred forty-one proteins were identified, and out of these, 64 proteins were predicted to be secreted. We also identified the regulation of several virulence factors. Among the results, we highlight Cyb5 as a secreted molecule of Paracoccidioides in the exoproteome obtained during Fe deprivation. Cyb5 is described as necessary for the Fe deprivation response of Saccharomyces cerevisiae and Aspergillus fumigatus. Experimental data and molecular modeling indicated that Cyb5 can bind to Fe ions in vitro, suggesting that it can be relevant in the arsenal of molecules related to iron homeostasis in P. brasiliensis.
Insights
Paracoccidioides brasiliensis responds to iron deficiency by secreting proteins, including Cyb5, which binds iron. This study reveals new insights into fungal iron homeostasis and virulence factors during infection.
Area of Science:
- Mycology
- Infectious Diseases
- Biochemistry
Background:
- Paracoccidioides fungi cause paracoccidioidomycosis, a systemic mycosis.
- The host environment presents nutrient limitations, particularly iron (Fe), essential for fungal survival.
- Previous research identified fungal strategies for iron acquisition, but gaps remain in understanding metal deprivation responses.
Purpose of the Study:
- To investigate the exoproteome of Paracoccidioides brasiliensis under iron deprivation.
- To identify secreted proteins and potential virulence factors involved in iron homeostasis.
- To explore the role of Cyb5 in the iron deprivation response of Paracoccidioides.
Main Methods:
- Obtaining the exoproteome of Paracoccidioides brasiliensis (Pb18) under iron-limited conditions.
- Utilizing nanoUPLC-MS/E for high-throughput protein identification.
- Employing experimental assays and molecular modeling to assess Cyb5's iron-binding capabilities.
Main Results:
- Identified 141 proteins in the exoproteome, with 64 predicted as secreted.
- Observed the regulation of several virulence factors in response to iron deprivation.
- Highlighted Cyb5 as a secreted protein in iron-deprived Paracoccidioides, demonstrating in vitro iron-binding capacity.
Conclusions:
- Cyb5 is a secreted molecule in Paracoccidioides brasiliensis during iron deprivation.
- Cyb5's iron-binding ability suggests a significant role in maintaining iron homeostasis in this fungal pathogen.
- This study contributes to understanding fungal adaptation to iron-limited environments and identifies potential therapeutic targets.
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