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Author Spotlight: Quantifying Siderophores and Pyochelin for Infection Control
Published on: March 15, 2024
Molecular characterization of siderophore biosynthesis in Paracoccidioides brasiliensis
Marielle Garcia Silva1,2, Juliana Santana de Curcio1, Mirelle Garcia Silva-Bailão1
1Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, ICB II, Campus II, Universidade Federal de Goiás, Goiânia, GO Brazil.
Abstract:
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.
Insights
Pathogenic fungi like Paracoccidioides brasiliensis utilize siderophores for iron acquisition. This study shows P. brasiliensis can block its own siderophore production when external siderophores are available, impacting fungal virulence.
Area of Science:
- Medical Mycology
- Molecular Biology
- Pathogen-Host Interactions
Background:
- Iron is crucial for fungal pathogens, including Paracoccidioides spp., for successful infection.
- Fungal pathogens have evolved high-affinity iron uptake systems, such as siderophore production, to overcome host-imposed iron deprivation.
- Paracoccidioides spp. possess genes for hydroxamate siderophore biosynthesis and transport, induced under iron-limiting conditions.
Purpose of the Study:
- To investigate the regulation of siderophore biosynthesis in Paracoccidioides brasiliensis in response to environmental iron availability.
- To determine the role of siderophores in the virulence of Paracoccidioides spp.
Main Methods:
- Quantitative analysis of SidA enzyme expression (RNA and protein levels) in response to ferrioxamine B (FOB).
- Assay of SidA enzyme activity in the presence of FOB.
- Generation of silenced Paracoccidioides brasiliensis mutants (AsSidA) using antisense RNA technology.
- Assessment of siderophore production and virulence in AsSidA strains.
Main Results:
- Addition of the xenosiderophore ferrioxamine B repressed SidA expression and activity in P. brasiliensis.
- AsSidA mutant strains showed reduced siderophore biosynthesis under iron deprivation.
- AsSidA mutant strains exhibited decreased virulence in an invertebrate model.
Conclusions:
- Paracoccidioides brasiliensis can suppress its endogenous siderophore biosynthesis when external siderophores are available, indicating a flexible iron scavenging strategy.
- Siderophore biosynthesis, specifically SidA, plays a significant role in the virulence of Paracoccidioides spp.
