ArticlePLoS neglected tropical diseases2017
Comparative genomics of Cryptococcus neoformans var. grubii associated with meningitis in HIV infected and uninfected patients in Vietnam.
Article in PLoS neglected tropical diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Single nucleotide polymorphisms are associated with strain-specific virulence differences among clinical isolates of Cryptococcus neoformans.Nature communications · 2024Pooled it
- Trial
- Vaccine-Mediated Protection of Mice Against African and Asian Clinical Strains ofJournal of fungi (Basel, Switzerland) · 2025Article
- Intrinsic and extrinsic factors affecting the evolution of virulence in the HIV-associated opportunistic human fungal pathogenVirulence · 2025Article
- Cryptococcal nutrient acquisition and pathogenesis: dining on the host.Microbiology and molecular biology reviews : MMBR · 2025Review
- Molecular Diagnostics ofDiseases (Basel, Switzerland) · 2024Review
- Cryptococcal meningitis.Nature reviews. Disease primers · 2023Review
- Unbiased discovery of natural sequence variants that influence fungal virulence.Cell host & microbe · 2023Article
- Importance of Clinical Isolates inJournal of fungi (Basel, Switzerland) · 2023Review
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- Article
- Review
- Epidemiological and Clinical Characteristics, Antifungal Susceptibility, and MLST-Based Genetic Analysis ofJournal of fungi (Basel, Switzerland) · 2022Article
- Deciphering the Association among Pathogenicity, Production and Polymorphisms of Capsule/Melanin in Clinical Isolates ofJournal of fungi (Basel, Switzerland) · 2022Article
- Evaluation of the Performance of a Multiplex Real-Time PCR Assay for the Identification ofInfection and drug resistance · 2022Article
- Associations betweenJournal of fungi (Basel, Switzerland) · 2021Review
- Molecular epidemiology and antifungal susceptibilities of Cryptococcus species isolates from HIV and non-HIV patients in Southwest China.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2021Article
- Cryptococcal Virulence in Humans: Learning From Translational Studies With Clinical Isolates.Frontiers in cellular and infection microbiology · 2021Review
- Molecular Markers Reveal Epidemiological Patterns and Evolutionary Histories of the Human PathogenicFrontiers in cellular and infection microbiology · 2021Review
- Assessing the virulence of Cryptococcus neoformans causing meningitis in HIV infected and uninfected patients in Vietnam.Medical mycology · 2020Article
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
The vast burden of cryptococcal meningitis occurs in immunosuppressed patients, driven by HIV, and is caused by Cryptococcus neoformans var. grubii. We previously reported cryptococcal meningitis in Vietnam arising atypically in HIV uninfected, apparently immunocompetent patients, caused by a single amplified fragment length polymorphism (AFLP) cluster of C. neoformans var. grubii (VNIγ). This variant was less common in HIV infected individuals; it remains unclear why this lineage is associated with apparently immunocompetent patients. To study this host tropism we aimed to further our understanding of clinical phenotype and genomic variation within Vietnamese C. neoformans var. grubii. After performing MLST on C. neoformans clinical isolates we identified 14 sequence types (STs); ST5 correlated with the VNIγ cluster. We next compared clinical phenotype by lineage and found HIV infected patients with cryptococcal meningitis caused by ST5 organisms were significantly more likely to have lymphadenopathy (11% vs. 4%, p = 0.05 Fisher's exact test) and higher blood lymphocyte count (median 0.76 versus 0.55 X109 cells/L, p = 0.001, Kruskal-Wallis test). Furthermore, survivors of ST5 infections had evidence of worse disability outcomes at 70 days (72.7% (40/55) in ST5 infections versus 57.1% (52/91) non-ST5 infections (OR 2.11, 95%CI 1.01 to 4.41), p = 0.046). To further investigate the relationship between strain and disease phenotype we performed genome sequencing on eight Vietnamese C. neoformans var. grubii. Eight genome assemblies exhibited >99% nucleotide sequence identity and we identified 165 kbp of lineage specific to Vietnamese isolates. ST5 genomes harbored several strain specific regions, incorporating 19 annotated coding sequences and eight hypothetical proteins. These regions included a phenolic acid decarboxylase, a DEAD-box ATP-dependent RNA helicase 26, oxoprolinases, a taurine catabolism dioxygenase, a zinc finger protein, membrane transport proteins and various drug transporters. Our work outlines the complexity of genomic pathogenicity in cryptococcal infections and identifies a number of gene candidates that may aid the disaggregation of the pathways associated with the pathogenesis of Cryptococcus neoformans var. grubii.
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