How metals fuel fungal virulence, yet promote anti-fungal immunity

Alanoud Alselami, Rebecca A. Drummond*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Abstract

Invasive fungal infections represent a significant global health problem, and present several clinical challenges, including limited treatment options, increasing rates of antifungal drug resistance and compounding comorbidities in affected patients. Metals, such as copper, iron and zinc, are critical for various biological and cellular processes across phyla. In mammals, these metals are important determinants of immune responses, but pathogenic microbes, including fungi, also require access to these metals to fuel their own growth and drive expression of major virulence traits. Therefore, host immune cells have developed strategies to either restrict access to metals to induce starvation of invading pathogens or deploy toxic concentrations within phagosomes to cause metal poisoning. In this Review, we describe the mechanisms regulating fungal scavenging and detoxification of copper, iron and zinc and the importance of these mechanisms for virulence and infection. We also outline how these metals are involved in host immune responses and the consequences of metal deficiencies or overloads on how the host controls invasive fungal infections.
Original languageEnglish
Article numberdmm050393
Number of pages12
JournalDisease Models & Mechanisms
Volume16
Issue number10
DOIs
Publication statusPublished - 31 Oct 2023

Bibliographical note

Funding:
We would like to thank the Medical Research Council (MR/S024611) and the Saudi Arabian government for funding. A.A. is supported by a PhD scholarship awarded by the Saudi Arabian Cultural Bureau.

Keywords

  • Copper
  • Iron
  • Macrophage
  • Nutritional immunity
  • Fungal immunology

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