Crosstalk between iron and flavins in the opportunistic fungal pathogen Candida albicans

Marika S David1, Zhengkai Zhu1, Maranda R McDonald1

  • 1The Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.

Insights

Candida albicans secretes riboflavin during iron starvation, which enhances iron uptake. This adaptation helps the fungus survive in iron-limited host environments.

Area of Science:

  • Microbiology
  • Mycology
  • Biochemistry

Background:

  • The host immune system restricts iron (Fe) availability to pathogens.
  • Candida albicans, a fungal pathogen, has mechanisms to cope with Fe-limitation.
  • Flavin secretion is an observed response, but its purpose and regulation are unclear.

Purpose of the Study:

  • To identify the flavin secreted by Fe-starved C. albicans.
  • To investigate the impact of Fe-starvation on intracellular flavin pools.
  • To determine the role of extracellular flavins in Fe acquisition.

Main Methods:

  • High-performance liquid chromatography (HPLC) and mass spectrometry were used to analyze flavins.
  • Gene expression analysis related to flavin biosynthesis and metabolism was performed.
  • Fe uptake assays were conducted using C. albicans in animal serum.

Main Results:

  • Riboflavin was identified as the sole flavin secreted by Fe-starved C. albicans.
  • Fe-starvation increased intracellular riboflavin levels, while FAD and FMN remained unchanged.
  • The transcription factor Sef1 regulates riboflavin biosynthesis, export, and Fe uptake.

Conclusions:

  • Extracellular riboflavin enhances Fe uptake by C. albicans, likely via redox activity.
  • This riboflavin-mediated Fe acquisition mechanism promotes fungal fitness in Fe-limited host environments.

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