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Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans
Published on: December 19, 2014
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Three phylogenetic groups have driven the recent population expansion of Cryptococcus neoformans
P M Ashton1,2, L T Thanh1, P H Trieu1
1Wellcome Trust Asia Programme, Oxford University Clinical Research Unit, 764 Vo Van Kiet, Ho Chi Minh City, Vietnam.
Nature Communications
|May 4, 2019
Summary
Cryptococcus neoformans, a major cause of HIV-associated deaths, shows recent population expansion driven by three sub-clades. These sub-clades (VNIa-4, VNIa-5, VNIa-93) exhibit different geographic prevalence and clinical outcomes.
Area of Science:
- * Mycology and Infectious Diseases
- * Genomics and Population Genetics
- * HIV/AIDS Pathogenesis
Background:
- * Cryptococcus neoformans (C. neoformans var. grubii) is an opportunistic fungal pathogen responsible for significant mortality in individuals with HIV/AIDS.
- * An estimated 181,000 HIV-associated deaths occur annually due to C. neoformans infections.
- * Understanding the population dynamics and genetic diversity of C. neoformans is crucial for public health interventions.
Purpose of the Study:
- * To investigate the population structure and evolutionary history of C. neoformans isolates from HIV-infected patients in Asia and Africa.
- * To identify the specific lineages driving recent population expansion.
- * To explore the association between C. neoformans sub-clades and clinical outcomes in different geographic regions.
Main Methods:
- * Whole-genome sequencing of 699 C. neoformans isolates primarily from HIV-infected patients across five countries in Asia and Africa.
- * Phylogenetic analysis to reconstruct the evolutionary relationships and population expansion patterns.
- * Integration of genomic data with clinical information to correlate sub-clade with patient outcomes.
Main Results:
- * Phylogenetic analysis revealed a recent exponential population expansion of C. neoformans.
- * Three specific sub-clades within the VNIa lineage (VNIa-4, VNIa-5, and VNIa-93) were identified as the primary drivers of this expansion, accounting for 91% of clinical isolates.
- * The VNIa-93 sub-clade, prevalent in Uganda and Malawi, was associated with better clinical outcomes compared to VNIa-4 and VNIa-5, which are predominant in Southeast Asia.
Conclusions:
- * The dominance of specific C. neoformans sub-clades (VNIa-4, VNIa-5, VNIa-93) in clinical settings suggests significant adaptive evolution.
- * Geographic variation in sub-clade prevalence and their differential association with clinical outcomes highlight the need for region-specific strategies.
- * Further research is warranted to elucidate the mechanisms underlying sub-clade dominance and the genotype-phenotype correlations in C. neoformans infections.
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