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Background <p>A substantial rise in the less common <i>Trichophyton tonsurans</i> in India with notable multi-drug resistance has transformed into a reason for recalcitrant dermatophytosis and concern.</p> Methods and results <p>In the current investigation, we isolated ‘resistant’ strains of <i>T. tonsurans</i> from clinical samples and studied the transcriptional modulation of the drug efflux transporter genes upon challenge with sub-lethal doses of various antifungal agents. Antifungal susceptibility and MIC determination were conducted following the CLSI M38-A2 protocol on clinical samples obtained from patients with superficial mycoses. Molecular identification was conducted through ribosomal DNA (rDNA) ITS sequencing. Both ‘sensitive’ and ‘resistant’ strains were challenged with sub-inhibitory concentration (70% MIC) of Fluconazole, Itraconazole, Posaconazole and Terbinafine followed by RNA-seq analysis using Illumina NextSeq 550 system. The RNA-seq data were validated by RT-qPCR. <i>T. tonsurans</i> presented 50 cases of dermatophytosis with 09 ‘resistant’ strains. Minimum inhibitory concentrations (MIC) of Fluconazole, Itraconazole, Posaconazole and Terbinafine were 74.80, 0.08, 0.01 and 0.53&#xa0;µg/mL respectively. Total 88 drug transporter genes were differentially expressed. MFS transporter genes were up-regulated more than the ABC transporters. Prominent up-regulation was witnessed in ‘resistant’ than ‘sensitive’ groups. Terbinafine-treated groups demonstrated highest up-regulation of MDR genes. RT-qPCR experiments yielded similar data showing a strong correlation (<i>r</i> &gt; 0.90, <i>p</i> &lt; 0.001).</p> Conclusions <p>The findings of the study emphasize transcriptional modulation of all transporter genes of <i>T. tonsurans</i>, annotated till date, in response to antifungal challenge, confirming the need to identify multi-drug resistance and select the treatment strategy wisely. It also calls for conducting further sequencing-based studies on <i>T. tonsurans</i>.</p>

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Clinical isolates of the anthropophilic dermatophyte Trichophyton tonsurans exhibit transcriptional regulation of multidrug efflux transporters that induce antifungal resistance

  • 期刊论文

  • 发表日期：

    2025年6月18日

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  • Suman Samaddar,
  • Moqbel Ali Moqbel Redhwan,
  • Mohan Muttanahally Eraiah,
  • Raju Koneri

摘要

Background

A substantial rise in the less common Trichophyton tonsurans in India with notable multi-drug resistance has transformed into a reason for recalcitrant dermatophytosis and concern.

Methods and results

In the current investigation, we isolated ‘resistant’ strains of T. tonsurans from clinical samples and studied the transcriptional modulation of the drug efflux transporter genes upon challenge with sub-lethal doses of various antifungal agents. Antifungal susceptibility and MIC determination were conducted following the CLSI M38-A2 protocol on clinical samples obtained from patients with superficial mycoses. Molecular identification was conducted through ribosomal DNA (rDNA) ITS sequencing. Both ‘sensitive’ and ‘resistant’ strains were challenged with sub-inhibitory concentration (70% MIC) of Fluconazole, Itraconazole, Posaconazole and Terbinafine followed by RNA-seq analysis using Illumina NextSeq 550 system. The RNA-seq data were validated by RT-qPCR. T. tonsurans presented 50 cases of dermatophytosis with 09 ‘resistant’ strains. Minimum inhibitory concentrations (MIC) of Fluconazole, Itraconazole, Posaconazole and Terbinafine were 74.80, 0.08, 0.01 and 0.53 µg/mL respectively. Total 88 drug transporter genes were differentially expressed. MFS transporter genes were up-regulated more than the ABC transporters. Prominent up-regulation was witnessed in ‘resistant’ than ‘sensitive’ groups. Terbinafine-treated groups demonstrated highest up-regulation of MDR genes. RT-qPCR experiments yielded similar data showing a strong correlation (r > 0.90, p < 0.001).

Conclusions

The findings of the study emphasize transcriptional modulation of all transporter genes of T. tonsurans, annotated till date, in response to antifungal challenge, confirming the need to identify multi-drug resistance and select the treatment strategy wisely. It also calls for conducting further sequencing-based studies on T. tonsurans.