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Genetic diversity and microevolution in clinical Cryptococcus isolates from Cameroon.

Poppy Sephton-Clark¹, Elvis Temfack^2,3, Jennifer L Tenor⁴

¹Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

Medical Mycology

|November 12, 2023

Summary

This summary is machine-generated.

Cryptococcal meningitis genetic diversity varies between Malawi and Cameroon. Cryptococcus isolates show microevolution and mixed infections during HIV/AIDS treatment.

Keywords:

Cryptococcus GWAS genome sequencing intrahost diversity phylogeography

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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.