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Hydroxamate production as a high affinity iron acquisition mechanism in Paracoccidioides spp

Mirelle Garcia Silva-Bailão1, Elisa Flávia Luiz Cardoso Bailão2, Beatrix Elisabeth Lechner3

  • 1Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil; Programa de Pós-Graduação em Patologia Molecular, Universidade de Brasília, Brasília, Brazil.

Plos One
|August 27, 2014
PubMed

Insights

Paracoccidioides fungi produce and use siderophores to acquire iron, crucial for survival in iron-limited environments like mammalian hosts. This iron uptake mechanism is linked to the fungus

Area of Science:

  • Medical Mycology
  • Microbial Physiology
  • Biochemistry

Background:

  • Iron is essential for fungal growth but often scarce in host environments.
  • Pathogenic fungi develop high-affinity iron acquisition systems, including siderophore production and uptake.
  • Paracoccidioides species cause systemic mycosis, necessitating investigation into their iron acquisition strategies.

Purpose of the Study:

  • To investigate the role of siderophores in iron acquisition by Paracoccidioides.
  • To identify siderophores produced and utilized by Paracoccidioides.
  • To assess the contribution of siderophores to Paracoccidioides pathogenicity during host-pathogen interactions.

Main Methods:

  • Gene expression analysis under iron starvation.
  • High-performance liquid chromatography (HPLC) for siderophore identification.
  • Growth assays using siderophores as sole iron source.
  • Co-cultivation with macrophages to assess survival.
  • Cross-feeding experiments with Aspergillus nidulans.

Main Results:

  • Iron starvation induces siderophore biosynthesis and transport genes in Paracoccidioides.
  • Paracoccidioides produces and secretes coprogen B, with dimerumic acid as a breakdown product.
  • Intracellular siderophores include ferricrocin and ferrichrome C.
  • The fungus utilizes exogenous siderophores, including ferrioxamine, for growth.
  • Exogenous siderophores enhance Paracoccidioides survival during macrophage co-cultivation.
  • Paracoccidioides siderophores support the growth of siderophore-deficient Aspergillus nidulans.

Conclusions:

  • Paracoccidioides synthesizes and utilizes siderophores to overcome iron limitation.
  • Siderophore production is a key mechanism for Paracoccidioides survival and potential pathogenicity within the host.
  • This study elucidates a critical iron acquisition pathway contributing to fungal virulence.

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