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Record W4313544669 · doi:10.1073/pnas.2217111120

Similar evolutionary trajectories in an environmental <i>Cryptococcus neoformans</i> isolate after human and murine infection

2023· article· en· W4313544669 on OpenAlexfundno aff
Poppy Sephton-Clark, Scott A. McConnell, Nina T. Grossman, Rosanna P. Baker, Quigly Dragotakes, Yunfan Fan, Man Shun Fu, Gracen R. Gerbig, Seth Greengo, J. Marie Hardwick, Madhura Kulkarni, Stuart M. Levitz, Joshua D. Nosanchuk, Shmuel Shoham, Daniel F. Q. Smith, Piotr R. Stempinski, Winston Timp, Maggie P. Wear, Christina A. Cuomo, Arturo Casadevall

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2023
Typearticle
Languageen
FieldMedicine
TopicFungal Infections and Studies
Canadian institutionsnot available
FundersDivision of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious DiseasesNational Heart, Lung, and Blood InstituteU.S. Department of Health and Human ServicesNational Institutes of HealthNational Institute of Allergy and Infectious DiseasesBroad InstituteNational Institute of Neurological Disorders and StrokeCanadian Institute for Advanced Research
KeywordsBiologyVirulenceCryptococcus neoformansFrameshift mutationGeneNonsynonymous substitutionPhenotypeGeneticsGenomeMicrobiologyWhole genome sequencingStrain (injury)Virology

Abstract

fetched live from OpenAlex

recovered from an immunocompromised patient with cryptococcosis based on molecular analyses available in 2000. Here, we report whole genome sequence analysis of the clinical and cockatoo strains. Both are closely related MATα strains belonging to the VNII lineage, confirming that the human infection likely originated from pet bird exposure. The two strains differ by 61 single nucleotide polymorphisms, including eight nonsynonymous changes involving seven genes. To ascertain whether changes in these genes are selected for during mammalian infection, we passaged the cockatoo strain in mice. Remarkably, isolates obtained from mouse tissue possess a frameshift mutation in one of the seven genes altered in the human sample (LQVO5_000317), a gene predicted to encode an SWI-SNF chromatin-remodeling complex protein. In addition, both cockatoo and patient strains as well as mouse-passaged isolates obtained from brain tissue had a premature stop codon in a homologue of ZFC3 (LQVO5_004463), a predicted single-zinc finger containing protein, which is associated with larger capsules when deleted and reverted to a full-length protein in the mouse-passaged isolates obtained from lung tissue. The patient strain and mouse-passaged isolates show variability in virulence factors, with differences in capsule size, melanization, rates of nonlytic expulsion from macrophages, and amoeba predation resistance. Our results establish that environmental strains undergo genomic and phenotypic changes during mammalian passage, suggesting that animal virulence can be a mechanism for genetic change and that the genomes of clinical isolates may provide a readout of mutations acquired during infection.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.192
Threshold uncertainty score0.201

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.031
GPT teacher head0.307
Teacher spread0.276 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations21
Published2023
Admission routes1
Has abstractyes

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