The synergistic antifungal effects of sodium phenylbutyrate combined with azoles against <i>Candida albicans</i> via the regulation of the Ras–cAMP–PKA signalling pathway and virulence
Bibliographic record
Abstract
The pathogenic fungus Candida albicans is one of the most commonly clinically isolated fungal species, and its resistance to the antifungal drug fluconazole is known to be increasing. In this paper, we sought to characterize the effect of sodium phenylbutyrate used alone or in combination with azoles against resistant C. albicans. The minimum inhibitory concentrations and sessile minimum inhibitory concentrations were determined to explore the synergistic mechanism. The results showed that sodium phenylbutyrate exerted clear antifungal activity and that the combination of sodium phenylbutyrate and azoles functioned synergistically to combat resistant C. albicans. In our study of the mechanism, we initially found that the combination therapy resulted in the inhibition of hypha growth, the increased penetration of fluconazole through C. albicans biofilm, and the decreased expression of hyphae-related genes and the upstream regulatory genes (CYR1 and TPK2) of the Ras-cAMP-PKA signalling pathway, as determined by RT-PCR. In addition, the combination treatment decreased the extracellular phospholipase activities and the expression of aspartyl proteinase genes (SAP1-SAP3). The synergistic antifungal effects of the combination of sodium phenylbutyrate and azoles against resistant C. albicans was mainly based on the regulation of the Ras-cAMP-PKA signalling pathway, hyphae-related genes, and virulence factors.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| 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".