Evidence mapPaperPMID 41544091Full record

ArticlePLoS genetics2026

Temperature and genetic background drive mobilization of diverse transposable elements in a global human fungal pathogen.

Anna I Mackey, Vesper Fraunfelter, Samantha Shaltz, John McCormick, Callan Schroeder, John R Perfect, Cedric Feschotte, Paul M Magwene, Asiya Gusa

Abstract read
In one paragraph

Article in PLoS genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Anna I MackeyDepartment of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America.ORCID https://orcid.org/0000-0001-9263-1659
Vesper FraunfelterDepartment of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America.ORCID https://orcid.org/0009-0009-1454-5443
Samantha ShaltzDepartment of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America.ORCID https://orcid.org/0009-0006-3509-2277
John McCormickDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
Callan SchroederDepartment of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America.ORCID https://orcid.org/0009-0007-3824-1757
John R PerfectDepartment of Medicine, Duke University, Durham, North Carolina, United States of America.
Cedric FeschotteDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
Paul M MagweneDepartment of Biology, Duke University, Durham, North Carolina, United States of America.ORCID https://orcid.org/0000-0002-7659-2589
Asiya GusaDepartment of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America.ORCID https://orcid.org/0000-0001-9915-1834

Funding

Tri-Institutional Molecular Mycology and Pathogenesis Training ProgramT32AI052080 · NIAID · DUKE UNIVERSITY · PI ANDREW ALSPAUGH, JOSEPH HEITMAN · 2003 to 2026
$8.7M
The Genetic Basis of Virulence in Cryptococcus NeoformansR01AI133654 · NIAID · DUKE UNIVERSITY · PI JOSEPH HEITMAN, Paul Mitaari Magwene · 2017 to 2026
$4.7M
Regulation of mitotic genome stability in yeast.R35GM118077 · NIGMS · DUKE UNIVERSITY · PI JINKS-ROBERTSON, SUE · 2016 to 2023
$4.5M
Pathobiology of C. neoformans in the Central Nervous SystemR01AI073896 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 2008 to 2018
$4.4M
Genomic and Physiological Impact of Transposable Elements.R35GM122550 · NIGMS · CORNELL UNIVERSITY · PI Cedric Feschotte · 2017 to 2026
$4.4M
Evolution of Cryptococcus neoformans Strains from Patients with HIV/AIDSR01AI093257 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 2011 to 2022
$3.8M
Stress-induced transposon mobilization in the human fungal pathogen CryptococcusR00AI166094 · NIAID · DUKE UNIVERSITY · PI GUSA, ASIYA · 2024 to 2025
$498k
Stress-induced transposon mobilization in the human fungal pathogen CryptococcusK99AI166094 · NIAID · DUKE UNIVERSITY · PI GUSA, ASIYA · 2022 to 2023
$197k
NIAID NIH HHS K99 AI166094NIAID NIH HHS R00 AI166094NIAID NIH HHS R01 AI073896NIAID NIH HHS R01 AI093257NIAID NIH HHS R01 AI133654NIAID NIH HHS T32 AI052080NIGMS NIH HHS R35 GM118077NIGMS NIH HHS R35 GM122550
6 · The paper itself

Abstract

Transposable elements (TEs) are key agents of genome evolution across all domains of life. These mobile genetic elements can cause mutations through transposition or by promoting structural rearrangements. Stress conditions can amplify TE mobility, either by impairing TE suppression mechanisms or through stress-induced interactions between transcription factors and TE sequences, offering a route for rapid genetic change. As such, TEs represent an important source of adaptability within populations. To investigate the interplay between environmental stress and eukaryotic TE dynamics relevant to infectious disease, we examined how heat stress and host-mimicking medium (RPMI) affect TE mobility in the global human fungal pathogen Cryptococcus neoformans, using a collection of clinical and environmental isolates. Using a selection-based screen, we captured the mobilization of seven distinct mobile element families, encompassing diverse retrotransposons and DNA transposons, whose insertions conferred antifungal resistance. This includes a novel element, CNEST, which belongs to the CACTA, Mirage, Chapaev (CMC) supergroup. Heat stress at human body temperature (37°C) significantly increased the mobilization of a subset of these TEs, leading to higher rates of acquired antifungal resistance. Whole-genome assemblies revealed that, compared to retrotransposons, DNA transposons were hypomethylated and approximately uniformly distributed throughout the genome, features that may contribute to their frequent mobilization. We further assessed TE-driven genomic changes within hosts using serial isolates from patients with recurrent cryptococcal infections and from isolates passaged through mice. While we observed evidence of TE copy number changes near chromosome ends, we found no indication of TE-mediated alterations near gene-coding regions across any of the serial isolates. Finally, TE mobility was isolate- and strain-dependent, with significant variation even among clonally related strains collected from the same patient, emphasizing the role of genetic background in shaping TE activity. Together, these findings reveal a complex and dynamic relationship between environmental stress, genetic background, TE type-specific epigenetic regulation, and TE mobility, with important implications for adaptation and acquired antifungal resistance in C. neoformans.

Indexed as

Cryptococcus neoformansDNA Transposable ElementsCryptococcosisDrug Resistance, FungalEvolution, MolecularGenome, FungalHeat-Shock ResponseHumansRetroelementsTemperatureDNA Transposable ElementsRetroelements

Identifiers

PMID41544091
PMCPMC12810828

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.