When antifungals stop working: virulence and drug resistance in emerging dermatophyte infections

About the project

About the Project A new generation of drug-resistant fungal skin pathogens is spreading worldwide. We don't know why they are so aggressive — this project aims to find out. Dermatophytes infect the skin, hair and nails of 20–25% of the world's population, making them the most common fungal pathogens of humans. Treatment takes often a long time, but very problematic in very recent years is the rise of drug-resistant dermatophytes. Trichophyton indotineae , first identified in South Asia and now reported across Europe, the Middle East, Africa and North America, causes extensive, highly inflammatory and disfiguring infections that resist terbinafine — the first-line treatment — due to mutations in the squalene epoxidase gene. Patients relapse repeatedly and clinicians are running out of options. Yet its close relative T. rubrum causes only chronic, low-grade disease. Why closely related species differ so dramatically in virulence is unknown, and that is the gap this PhD will fill. The project You will compare how different dermatophyte species behave during infection of real skin tissue, using an ex vivo porcine skin model developed in our laboratory (Ho et al., 2020) that reproduces human skin architecture under controlled conditions. Human nail and lab-grown skin-equivalent models are also available. You will investigate: How rapidly and deeply each species invades skin tissue Whether aggressive species cause more damage to the stratum corneum Differences in keratin degradation and secretion of virulence-associated enzymes How each species alters its gene expression in response to the skin environment How these differences influence antifungal susceptibility and treatment failure Techniques include histology and microscopy, quantification of fungal burden and invasion depth, enzyme activity assays, and targeted gene expression analysis, building on our RNA-seq work in dermatophytes (Ho et al., 2025). There is scope to shape the project towards your own interests, whether imaging, molecular biology, biochemistry or drug resistance. What you will gain Specialist training in medical mycology and fungal infection models — a skill set in short international supply — alongside expertise in microscopy, histology, molecular and biochemical techniques, and quantitative data analysis. You will work with an established, published infection model you can carry into your own independent research, publish on a clinically urgent topic, and be supported to present at international conferences. Who we are looking for At least a good 2:1 (or international equivalent) in microbiology, biomedical science, biochemistry, pharmacy, medicine or a related subject. A master's degree and prior laboratory experience are advantageous but not essential. The project suits applicants interested in microbial pathogenesis, host–pathogen interactions, antimicrobial resistance or emerging infectious diseases. Contact Informal enquiries are strongly encouraged before applying. Email Dr Albert Bolhuis ( a.bolhuis@bath.ac.uk ) with a CV and a short note on your interest, and I will be glad to discuss the project, the group and the application process. Funding This project is open to self-funded students, including those supported by a government, employer or institutional scholarship. If you intend to apply for external funding, please contact us early — we can support your application. References Ho FK, Delgado-Charro MB, Bolhuis A. Evaluation of an Explanted Porcine Skin Model to Investigate Infection with the Dermatophyte Trichophyton rubrum . Mycopathologia. 2020;185(2):233–243. doi:10.1007/s11046-020-00438-9 Ho FK, Al-Tabtabai A, Nasereddin SM, Malallah OS, Lindsay MA, Jones SA, Bolhuis A. Antimicrobial effects and mechanisms of hydrogen sulphide against nail pathogens. Sci Rep. 2025;15(1):38241. doi:10.1038/s41598-025-22062-7

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