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Hypoxia and fungal pathogenesis: to air or not to air?
Nora Grahl1, Kelly M Shepardson, Dawoon Chung
1Department of Immunology and Infectious Diseases, Montana State University, Bozeman, Montana, USA.
Abstract:
Over the last 3 decades, the frequency of life-threatening human fungal infections has increased as advances in medical therapies, solid-organ and hematopoietic stem cell transplantations, an increasing geriatric population, and HIV infections have resulted in significant rises in susceptible patient populations. Although significant advances have been made in understanding how fungi cause disease, the dynamic microenvironments encountered by fungi during infection and the mechanisms by which they adapt to these microenvironments are not fully understood. As inhibiting and preventing in vivo fungal growth are main goals of antifungal therapies, understanding in vivo fungal metabolism in these host microenvironments is critical for the improvement of existing therapies or the design of new approaches. In this minireview, we focus on the emerging appreciation that pathogenic fungi like Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus are exposed to oxygen-limited or hypoxic microenvironments during fungal pathogenesis. The implications of these in vivo hypoxic microenvironments for fungal metabolism and pathogenesis are discussed with an aim toward understanding the potential impact of hypoxia on invasive fungal infection outcomes.
Insights
Fungal infections are rising due to increased susceptible populations. This review explores how pathogenic fungi adapt to low-oxygen environments, impacting treatment strategies for invasive fungal infections.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Pathogen Metabolism
Background:
- Life-threatening fungal infections have increased over 3 decades.
- Advances in medicine and immunocompromised populations contribute to rising susceptibility.
- Understanding fungal adaptation to host microenvironments is crucial for effective antifungal therapies.
Purpose of the Study:
- To review the implications of hypoxic microenvironments on fungal metabolism and pathogenesis.
- To highlight the impact of oxygen limitation on invasive fungal infection outcomes.
- To inform the development of novel antifungal strategies.
Main Methods:
- Literature review focusing on pathogenic fungi (Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus).
- Analysis of studies investigating fungal adaptation to in vivo microenvironments.
- Discussion of metabolic pathways affected by hypoxia during infection.
Main Results:
- Pathogenic fungi encounter oxygen-limited (hypoxic) conditions during infection.
- Hypoxia significantly influences fungal metabolism and virulence.
- Understanding these adaptations is key to improving antifungal treatments.
Conclusions:
- Hypoxic microenvironments are a critical factor in fungal pathogenesis.
- Targeting fungal adaptation to hypoxia offers a promising avenue for new therapies.
- Further research into fungal metabolism under hypoxia is warranted to combat invasive fungal infections.
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