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Label-Free Quantitative Proteomics Workflow for Discovery-Driven Host-Pathogen Interactions
Published on: October 20, 2020
Metals at the Host-Fungal Pathogen Battleground
Ritu Garg1, Marika S David1, Shuyi Yang1
1Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA;
Abstract:
Fungal infections continue to represent a major threat to public health, particularly with the emergence of multidrug-resistant fungal pathogens. As part of the innate immune response, the host modulates the availability of metals as armament against pathogenic microbes, including fungi. The transition metals Fe, Cu, Zn, and Mn are essential micronutrients for all life forms, but when present in excess, these same metals are potent toxins. The host exploits the double-edged sword of these metals, and will either withhold metal micronutrients from pathogenic fungi or attack them with toxic doses. In response to these attacks, fungal pathogens cleverly adapt by modulating metal transport, metal storage, and usage of metals as cofactors for enzymes. Here we review the current state of understanding on Fe, Cu, Zn, and Mn at the host-fungal pathogen battleground and provide perspectives for future research, including a hope for new antifungals based on metals.
Insights
Host immune systems and fungal pathogens engage in a battle over essential metals like iron (Fe), copper (Cu), zinc (Zn), and manganese (Mn). Understanding this metal interplay could lead to novel antifungal therapies.
Area of Science:
- Microbiology
- Immunology
- Biochemistry
Background:
- Fungal infections pose a significant public health threat, exacerbated by multidrug-resistant strains.
- The host immune system utilizes transition metals (Fe, Cu, Zn, Mn) as weapons against fungal pathogens.
- These metals are essential nutrients but toxic in excess, creating a double-edged sword for the host.
Purpose of the Study:
- To review the current understanding of the host-fungal pathogen interactions involving iron, copper, zinc, and manganese.
- To explore how fungi adapt to host-driven metal modulation.
- To provide perspectives for future research and the development of metal-based antifungals.
Main Methods:
- Literature review of existing research on metal homeostasis in host-pathogen interactions.
- Analysis of fungal adaptation mechanisms related to metal transport, storage, and cofactor utilization.
- Synthesis of current knowledge on the roles of Fe, Cu, Zn, and Mn in antifungal immunity.
Main Results:
- Hosts strategically withhold or provide toxic doses of metals to combat fungal infections.
- Fungal pathogens exhibit sophisticated strategies to manage metal availability, including transport and storage.
- Fungi utilize metals as essential cofactors for critical enzymes, adapting to host challenges.
Conclusions:
- The dynamic interplay between host metals and fungal adaptation is crucial in infectious diseases.
- Targeting metal metabolism in fungi presents a promising avenue for novel antifungal drug development.
- Further research into host-metal-fungi interactions could revolutionize antifungal strategies.
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