The First Isolation of Multiple Antifungal‐Drug‐Resistant <i>Trichophyton Rubrum</i> in China and the Novel Resistance Mechanism
Bibliographic record
Abstract
OBJECTIVES: This study reports the first isolation of a multidrug-resistant Trichophyton rubrum strain in China, characterizing its drug resistance profile and mechanisms. METHODS: The isolate was identified by internal transcribed spacer (ITS) sequencing and phylogenetic analysis. In vitro antifungal susceptibility testing (AFST) was performed according to the M38-A3 CLSI guideline to determine minimum inhibitory concentrations (MICs) against eight antifungals (terbinafine, itraconazole, fluconazole, amorolfine, griseofulvin, voriconazole, luliconazole and amphotericin B). Whole genome sequencing (WGS), transcriptome sequencing and qRT-PCR were performed to explore the resistance mechanism. RESULTS: The multidrug-resistant T. rubrum strain L-6424 was isolated from a Chinese patient with generalised tinea corporis/cruris, tinea unguium and tinea manuum. It exhibited elevated MICs to terbinafine (2 mg/L), itraconazole (0.5 mg/L), and amorolfine (0.5 mg/L). The phylogenetic tree based on genome-wide single nucleotide polymorphisms (SNPs) showed L-6424 is not a novel genotype of T. rubrum, with high genetic similarity (99.94%) with the reference strain (CBS 139224). There were three amino acid substitutions in the squalene epoxidase (SQLE), including the previously reported F397L and H440Y, as well as a newly discovered V105M, and one amino acid substitution in the CYP51A (R239C) was identified. Also, significant differences at the transcriptome level between the drug-resistant and sensitive strains were observed, and it was screened and found that CYP51A, TruMDR5 and TERG_08139 may be related to azole resistance. CONCLUSIONS: Drug-resistant T. rubrum has emerged in China, indicating the possibly increasing severity of antifungal resistance. The complex mechanism of multidrug-resistant dermophytes poses challenges to clinical treatment, needing more attention.
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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 | 0.000 |
| 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 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".