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Published on: July 19, 2021
Purine Acquisition and Synthesis by Human Fungal Pathogens
Jessica L Chitty1,2, James A Fraser3
1Australian Infectious Diseases Research Centre, School of Chemistry & Molecular Biosciences, the University of Queensland, St Lucia, Queensland 4072, Australia. j.chitty@uq.edu.au.
Abstract:
While members of the Kingdom Fungi are found across many of the world's most hostile environments, only a limited number of species can thrive within the human host. The causative agents of the most common invasive fungal infections are Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans. During the infection process, these fungi must not only combat the host immune system while adapting to dramatic changes in temperature and pH, but also acquire sufficient nutrients to enable growth and dissemination in the host. One class of nutrients required by fungi, which is found in varying concentrations in their environmental niches and the human host, is the purines. These nitrogen-containing heterocycles are one of the most abundant organic molecules in nature and are required for roles as diverse as signal transduction, energy metabolism and DNA synthesis. The most common life-threatening fungal pathogens can degrade, salvage and synthesize de novo purines through a number of enzymatic steps that are conserved. While these enable them to adapt to the changing purine availability in the environment, only de novo purine biosynthesis is essential during infection and therefore an attractive antimycotic target.
Insights
Fungi like Candida albicans must acquire nutrients, including purines, to cause infections. De novo purine biosynthesis is essential for fungal growth during infection, making it a key target for new antifungal drugs.
Area of Science:
- Medical Mycology
- Molecular Biology
- Biochemistry
Background:
- Invasive fungal infections are caused by species like Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans.
- Fungi must adapt to host environments, including immune defenses, temperature, and pH, while acquiring essential nutrients for growth and dissemination.
- Purines are vital nitrogen-containing heterocycles required for various cellular processes, including DNA synthesis and energy metabolism.
Purpose of the Study:
- To investigate the role of purine metabolism in fungal pathogenesis.
- To identify essential purine metabolic pathways during human fungal infections.
- To evaluate de novo purine biosynthesis as a potential target for antimycotic drug development.
Main Methods:
- Analysis of purine metabolism pathways in common fungal pathogens.
- Assessment of fungal nutrient acquisition strategies within the host environment.
- Identification of essential enzymatic steps in purine biosynthesis during infection.
Main Results:
- Fungal pathogens possess mechanisms to degrade, salvage, and synthesize purines.
- De novo purine biosynthesis is indispensable for fungal survival and proliferation within the human host.
- Enzymatic steps in de novo purine synthesis are conserved across major fungal pathogens.
Conclusions:
- De novo purine biosynthesis is a critical and conserved pathway for fungal pathogens during infection.
- Targeting de novo purine biosynthesis presents a promising strategy for developing novel antifungal therapies.
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