Drivers of diversification in fungal pathogen populations
Daniel Murante1, Deborah Ann Hogan1
1Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Abstract:
To manage and treat chronic fungal diseases effectively, we require an improved understanding of their complexity. There is an increasing appreciation that chronic infection populations are often heterogeneous due to diversification and drift, even within a single microbial species. Genetically diverse populations can contribute to persistence and resistance to treatment by maintaining cells with different phenotypes capable of thriving in these dynamic environments. In chronic infections, fungal pathogens undergo prolonged challenges that can drive trait selection to convergent adapted states through restricted access to critical nutrients, assault by immune effectors, competition with other species, and antifungal drugs. This review first highlights the various genetic and epigenetic mechanisms that promote diversity in pathogenic fungal populations and provide an additional barrier to assessing the actual heterogeneity of fungal infections. We then review existing studies of evolution and genetic heterogeneity in fungal populations from lung infections associated with the genetic disease cystic fibrosis. We conclude with a discussion of open research questions that, once answered, may aid in diagnosing and treating chronic fungal infections.
Insights
Understanding fungal population diversity is key to treating chronic fungal diseases. Genetic and epigenetic factors drive this heterogeneity, impacting treatment resistance and persistence.
Area of Science:
- Medical Mycology
- Evolutionary Biology
- Infectious Diseases
Background:
- Chronic fungal infections are complex and difficult to treat.
- Fungal populations exhibit genetic heterogeneity due to diversification and drift.
- This diversity can lead to treatment persistence and resistance.
Purpose of the Study:
- To review mechanisms promoting fungal diversity in chronic infections.
- To examine evolution and heterogeneity in fungal populations from cystic fibrosis lung infections.
- To identify research gaps for improved diagnosis and treatment.
Main Methods:
- Literature review of genetic and epigenetic mechanisms.
- Analysis of studies on fungal evolution in chronic infections.
- Focus on lung infections in cystic fibrosis patients.
Main Results:
- Genetic and epigenetic factors significantly contribute to fungal population heterogeneity.
- Heterogeneity presents a barrier to assessing and treating fungal infections.
- Studies in cystic fibrosis highlight the impact of environmental pressures on fungal evolution.
Conclusions:
- A deeper understanding of fungal heterogeneity is crucial for effective management of chronic diseases.
- Addressing genetic diversity is essential for overcoming treatment resistance.
- Further research is needed to translate these findings into clinical practice.
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