Genetic diversity and microevolution in clinical Cryptococcus isolates from Cameroon.
Cryptococcus
GWAS
genome sequencing
intrahost diversity
phylogeography
Journal
Medical mycology
ISSN: 1460-2709
Titre abrégé: Med Mycol
Pays: England
ID NLM: 9815835
Informations de publication
Date de publication:
01 Dec 2023
01 Dec 2023
Historique:
received:
22
08
2023
revised:
03
11
2023
accepted:
09
11
2023
medline:
17
12
2023
pubmed:
12
11
2023
entrez:
12
11
2023
Statut:
ppublish
Résumé
Cryptococcal meningitis is the second most common cause of death in people living with HIV/AIDS, yet we have a limited understanding of how cryptococcal isolates change over the course of infection. Cryptococcal infections are environmentally acquired, and the genetic diversity of these infecting isolates can also be geographically linked. Here, we employ whole genome sequences for 372 clinical Cryptococcus isolates from 341 patients with HIV-associated cryptococcal meningitis obtained via a large clinical trial, across both Malawi and Cameroon, to enable population genetic comparisons of isolates between countries. We see that isolates from Cameroon are highly clonal, when compared to those from Malawi, with differential rates of disruptive variants in genes with roles in DNA binding and energy use. For a subset of patients (22) from Cameroon, we leverage longitudinal sampling, with samples taken at days 7 and 14 post-enrollment, to interrogate the genetic changes that arise over the course of infection, and the genetic diversity of isolates within patients. We see disruptive variants arising over the course of infection in several genes, including the phagocytosis-regulating transcription factor GAT204. In addition, in 13% of patients sampled longitudinally, we see evidence for mixed infections. This approach identifies geographically linked genetic variation, signatures of microevolution, and evidence for mixed infections across a clinical cohort of patients affected by cryptococcal meningitis in Central Africa. Cryptococcal meningitis, caused by Cryptococcus, results in approximately half a million deaths per year globally. We compare clinical Cryptococcus samples from Cameroon and Malawi to explore the genetic diversity of these isolates. We find instances of mixed-strain infections and identify genetic variants arising in Cryptococcus over disease.
Autres résumés
Type: plain-language-summary
(eng)
Cryptococcal meningitis, caused by Cryptococcus, results in approximately half a million deaths per year globally. We compare clinical Cryptococcus samples from Cameroon and Malawi to explore the genetic diversity of these isolates. We find instances of mixed-strain infections and identify genetic variants arising in Cryptococcus over disease.
Identifiants
pubmed: 37952096
pii: 7408620
doi: 10.1093/mmy/myad116
pmc: PMC10709296
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MR/V033417/1
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI093257
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI110818
Pays : United States
Organisme : NIAID NIH HHS
ID : U19AI110818
Pays : United States
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.
Références
mBio. 2019 Jul 16;10(4):
pubmed: 31311883
Genetics. 2023 Aug 9;224(4):
pubmed: 37226893
Pediatrics. 2001 May;107(5):E66
pubmed: 11331716
Nat Genet. 2012 Jun 17;44(7):821-4
pubmed: 22706312
J Clin Invest. 2019 Mar 1;129(3):999-1014
pubmed: 30688656
G3 (Bethesda). 2017 Apr 3;7(4):1165-1176
pubmed: 28188180
Fly (Austin). 2012 Apr-Jun;6(2):80-92
pubmed: 22728672
J Clin Invest. 2020 Jul 1;130(7):3353-3360
pubmed: 32484459
Infect Immun. 2009 Oct;77(10):4345-55
pubmed: 19620339
Mol Ecol. 2017 Apr;26(7):1991-2005
pubmed: 27862555
mBio. 2010 May 18;1(1):
pubmed: 20689742
PLoS Pathog. 2012 Feb;8(2):e1002495
pubmed: 22383873
Bioinformatics. 2014 May 1;30(9):1312-3
pubmed: 24451623
Genetics. 2017 Sep;207(1):327-346
pubmed: 28679543
Infect Dis Clin North Am. 2006 Sep;20(3):507-44, v-vi
pubmed: 16984867
mBio. 2022 Nov 10;13(6):e0262622
pubmed: 36354332
Nat Commun. 2019 May 2;10(1):2035
pubmed: 31048698
Genome Res. 2017 Jul;27(7):1207-1219
pubmed: 28611159
Cell Host Microbe. 2011 Mar 17;9(3):243-251
pubmed: 21402362
mBio. 2012 Sep 25;3(5):
pubmed: 23015735
Emerg Infect Dis. 2012 Oct;18(10):1618-24
pubmed: 23017442
Lancet Infect Dis. 2022 Dec;22(12):1748-1755
pubmed: 36049486
mBio. 2017 Mar 7;8(2):
pubmed: 28270580
PLoS Genet. 2014 Apr 17;10(4):e1004261
pubmed: 24743168
Genetics. 2006 Apr;172(4):2223-38
pubmed: 16322524
N Engl J Med. 2018 Mar 15;378(11):1004-1017
pubmed: 29539274
Antimicrob Agents Chemother. 2015 Dec;59(12):7197-204
pubmed: 26324276
Genome Biol. 2011;12(1):R1
pubmed: 21205303
PLoS Pathog. 2019 Jun 27;15(6):e1007777
pubmed: 31247052
Curr Protoc Bioinformatics. 2013;43:11.10.1-11.10.33
pubmed: 25431634
Methods Mol Biol. 2023;2658:81-103
pubmed: 37024697
Front Cell Infect Microbiol. 2019 Nov 08;9:384
pubmed: 31788454
PLoS Negl Trop Dis. 2019 Nov 18;13(11):e0007812
pubmed: 31738768
G3 (Bethesda). 2013 Apr 9;3(4):675-686
pubmed: 23550133
mBio. 2020 Apr 28;11(2):
pubmed: 32345637
Mol Biol Evol. 2014 Jul;31(7):1929-36
pubmed: 24739305