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Genetic diversity and microevolution in clinical Cryptococcus isolates from Cameroon
Poppy Sephton-Clark1, Elvis Temfack2,3, Jennifer L Tenor4
1Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Medical Mycology
|November 12, 2023
Summary
Cryptococcal meningitis genetic diversity varies between Malawi and Cameroon. Cryptococcus isolates show microevolution and mixed infections during HIV/AIDS treatment.
Area of Science:
- Medical Microbiology
- Genomics
- Infectious Diseases
Background:
- Cryptococcal meningitis is a leading cause of death in individuals with HIV/AIDS.
- Understanding cryptococcal isolate evolution during infection is limited.
- Environmental acquisition and geographic origin influence cryptococcal genetic diversity.
Purpose of the Study:
- To compare population genetics of cryptococcal isolates between Malawi and Cameroon.
- To investigate genetic changes and diversity within patients during infection.
- To identify geographic-linked genetic variation and microevolutionary signatures.
Main Methods:
- Whole genome sequencing of 372 clinical Cryptococcus isolates from 341 patients with HIV-associated cryptococcal meningitis.
- Population genetic comparisons between isolates from Malawi and Cameroon.
- Longitudinal sampling (days 7 and 14) from 22 Cameroonian patients to study intra-patient evolution.
Main Results:
- Cameroonian isolates were more clonal than Malawian isolates.
- Differential rates of disruptive variants were observed in genes related to DNA binding and energy metabolism.
- Disruptive variants arose during infection in genes like GAT204.
- Mixed infections were detected in 13% of longitudinally sampled patients.
Conclusions:
- Geographically linked genetic variation and microevolutionary signatures were identified in cryptococcal meningitis.
- Evidence for mixed infections during the course of cryptococcal meningitis in Central Africa was found.
- Genetic diversity of Cryptococcus isolates impacts patient outcomes in HIV/AIDS.
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