Determinants of virulence in human dermatophytes

About the Project

Dermatophytes are the most prevalent fungal pathogens of humans and cause infections in approximately 20–25% of the world’s population. Despite their clinical importance, striking differences in virulence exist between closely related species. Dermatophytes infect keratinised tissues—specifically skin, hair, and nails—where they colonise and grow by utilising keratin as their primary nutrient source. While Trichophyton rubrum typically causes chronic, low‑grade infections, members of the T. mentagrophytes species complex—particularly the recently emerged Trichophyton indotineae—are associated with highly inflammatory, extensive, and difficult‑to‑treat disease. Of particular concern, T. indotineae also frequently exhibits resistance to first‑line antifungal therapies such as terbinafine, largely driven by mutations in the squalene epoxidase gene, further complicating treatment and contributing to persistent and recurrent infections. The biological basis for these differences in virulence and drug response remains poorly understood.

This PhD project aims to identify determinants of virulence by directly comparing infection behaviour, tissue damage, and pathogenic potential across multiple dermatophyte species. The project will address:

• How rapidly and extensively different species invade skin tissue
• Whether highly virulent species cause greater structural damage to the stratum Cornell
• Differences in keratin degradation and secretion of virulence‑associated enzymes
• Species‑specific transcriptional and phenotypic responses to the skin environment
• How differences in virulence affect susceptibility to antifungals

The work will focus on an established ex vivo porcine skin infection model (Ho et al., 2020), which closely mimics human skin architecture while allowing controlled experimental analysis of fungal behaviour. Other models may also be used, such as those based on human nails or lab-grown skin equivalents. Infections will be analysed using histology and microscopy, quantitative assessment of fungal burden and invasion depth, enzyme activity assays, and targeted gene expression analysis. Where relevant, transcriptomic approaches will be informed by our prior experience using RNA-seq to study antifungal responses in dermatophytes (Ho et al., 2025). Complementary in vitro assays will assess growth, stress tolerance, and keratin utilisation.

The student will gain training in medical mycology, fungal infection models, microscopy, molecular and biochemical techniques, and quantitative data analysis. The project addresses an emerging clinical problem and is well suited to a self‑funded PhD student with interests in microbial pathogenesis, host–pathogen interactions, or emerging infectious diseases.

Funding Notes

This project is open to self-funded students only, including those funded by their government or institution, or those with other means of supporting their studies.