Acidic pH Reduces Fluconazole Susceptibility in <i>Cryptococcus neoformans</i> by Altering Iron Uptake and Enhancing Ergosterol Biosynthesis
Why this work is in the frame
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Bibliographic record
Abstract
The opportunistic fungal pathogen Cryptococcus neoformans encounters diverse environmental pH conditions within the host.Hence, the ability to adapt to different pH levels plays a key role in survival and pathogenesis, although a full understanding of adaptation has yet to be achieved.In this study, we investigated how environmental pH influences antifungal drug susceptibility and iron uptake in C. neoformans.We found that acidic conditions significantly reduced the susceptibility of C. neoformans to the antifungal drug fluconazole.Moreover, iron acquisition in C. neoformans was independent of the high-affinity iron uptake system under acidic conditions, and lower pH increased the levels of intracellular iron, ergosterol, and heme, potentially accounting for the reduced susceptibility of the fungus to fluconazole.Transcriptome analysis further elucidated the mechanisms underlying the pH-dependent shift in iron uptake and antifungal susceptibility in C. neoformans.Overall, our findings highlight the importance of environmental pH in the physiology and pathogenesis of C. neoformans and provide insights to support the development of novel treatments for cryptococcosis.
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Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it