Combined genetic and environmental factors shape the landscape of anti-fungal tolerance in Nakaseomyces glabratus
Bibliographic record
Abstract
The rising incidence of fungal infections caused by Candida species is compounded by increasing antifungal resistance, compromising treatment efficacy. In Candida albicans, antifungal drug tolerance (AFDT) has emerged as a distinct, clinically relevant phenotype. However, AFDT remains underexplored in other clinically significant Candida species, and its prevalence across the genus is unclear. Here, we characterize AFDT in Nakaseomyces glabratus (formerly Candida glabrata), the second most common cause of candidiasis. Using disk diffusion and supra-MIC growth assays, we quantified AFDT across six clinical isolates and a reference strain. Our results mirror findings in C. albicans, demonstrating reproducible AFDT across N. glabratus strains in response to multiple azoles. Importantly, tolerance did not correlate with resistance profiles, underscoring AFDT as a distinct phenotype. Isolates were categorized into high- medium- and low-tolerance groups based on variability. Highly tolerant strains showed reduced clearance in a Galleria mellonella infection model, aligning with previous AFDT studies. Tolerance was modulated by environmental factors such as media, temperature, and azole, yet relative strain tolerance remained stable—suggesting a heritable, strain-specific trait shaped by genetic and environmental factors. These findings underscore the clinical relevance of AFDT in N. glabratus and support further investigation into its molecular underpinnings and therapeutic impact.
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How this classification was reachedexpand
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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".