Sterol-C4-methyl-oxidase Erg251 governs Candida albicans hypoxic growth, commensalism and virulence
Bibliographic record
Abstract
Intestinal-colonizing Candida albicans is a primary source of systemic infection where it translocates across intestinal barriers into the bloodstream leading to disseminated candidiasis. To persist in the gastrointestinal tract, C. albicans must adapt to complex environments, including extreme hypoxic conditions (EHC). Here, we performed a functional genomic screen to identify genes important for C. albicans fitness under EHC. We discovered that one of the two C. albicans sterol C4-methyl oxidases, Erg251, is specifically required for producing ergosterol, an essential component for fungal membrane, in low oxygen conditions. Deleting Erg251 or mutating key amino acid residues for its function under EHC impaired C. albicans virulence and colonization in mouse models of systemic infection and commensalism, respectively. Selective inhibitors of fungal sterol C4-methyl oxidases, inhibit C. albicans growth in vitro and in a nematode infection model, showing therapeutic potential. Candida albicans must adapt to hypoxia. Here, the authors discover the sterol C4-methyl oxidase (SMO) Erg251 is essential for extreme hypoxic growth, as well as virulence and colonization, and that SMO inhibitors have therapeutic potential.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".