PhD thesis defense in biomedical and pharmaceutical sciences by Bastien Tirtiaux

Mechanistic insights in the Malassezia hyphal form and its role in skin-pathogen interaction

Candidate

Bastien Tirtiaux

Promoters

Dr. Catherine Lambert de Rouvroit, UNamur, Department of medicine, Molecular Physiology Research Unit (URPhyM) - promoter

Prof. Yves Poumay, UNamur, Department of medicine, Molecular Physiology Research Unit (URPhyM) - co-promoter

Jury

• Prof. Benoît Muylkens, UNamur (president)
• Dr. Catherine Lambert de Rouvroit, UNamur (promoter)
• Prof. Yves Poumay, UNamur (co-promoter)
• Prof. Laure Dumoutier, UCLouvain
• Dr. Irène Gallais-Serezal, CHU Besançon, France
• Prof. Giuseppe Ianiri, University of Molise, Italy

Summary

Malassezia is a lipid-dependent basidiomycetous yeast of the skin microbiota that thrives in sebum-rich areas such as the scalp, chest and back. Although commensal, and potentially beneficial, Malassezia is also associated with skin disorders including atopic dermatitis, seborrheic dermatitis and pityriasis versicolor (PV). PV is characterized by a morphological switch from round-to-oval yeast cells to invasive hyphae. However, host responses to Malassezia hyphae remain unknown, as this phenotype has never been described on any infection model. Moreover, the molecular mechanisms driving hyphal growth are poorly understood. Here, we developed an in vitro infection model using reconstructed human epidermis (RHE) and found that only diploid strains, carrying both compatible mating-type (MAT) alleles, formed hyphae and invaded the cornified layer of RHE, mimicking PV histological sections. These strains caused marked barrier impairment and elicited strong keratinocyte responses that differed from those induced by yeast-forming strains. In addition, MAT-compatible haploid strains carrying distinct resistance markers were co-cultured on minimal medium supplemented with olive oil. This yielded double-drug-resistant fusion products that harbored MAT alleles from both parents and had acquired the ability to form invasive hyphae. Altogether, this work provides the first insight into host responses to Malassezia hyphae and links hyphal morphogenesis to mating, paving the way for a better understanding of Malassezia pathogenicity.