Identification and Functional Analysis of the Siderophore Transporter in the Skin-Associated fungus Malassezia

Iron is an essential element for the majority of organisms, serving as a cofactor in numerous cellular processes. Microorganisms have evolved diverse strategies for iron acquisition, including reductive iron assimilation and siderophore-mediated iron acquisition. Siderophores, low molecular mass ferric-iron chelators, are classified into different structural classes such as hydroxamates, catecholates, carboxylates, phenolates, and mixed classes. Fungal siderophores typically belong to the hydroxamates type. Fungi can synthesize their own siderophores or acquire them via siderophore transporters. In this study, we investigated iron acquisition mechanisms in the skin-associated fungus Malassezia restricta. By screening the genome of M. restricta, we identified two homologous genes, MRET_2650 and MRET_3788, which share sequence similarities with the Siderophore Iron Transporter (SIT) genes found in a model pathogenic fungus Cryptococcus neoformans. To investigate the expression patterns of these genes under iron-limited conditions, we performed quantitative reverse transcription-polymerase chain reaction analysis. As anticipated, we observed increased expression levels of MRET_2650 and MRET_3788 in the absence of iron, whereas expression levels did not show a significant increase in the presence of exogenous siderophores. To validate the functions of these genes, we conducted complementation tests using Saccharomyces cerevisiae lacking siderophore transporters. MRET_2650 successfully complemented the hydroxamate-type ferrichrome transporter in S. cerevisiae, indicating its involvement in siderophore-mediated iron acquisition. However, the precise substrate specificity of MRET_3788 remains to be elucidated, necessitating further investigation. Overall, our study provides valuable insights into the iron acquisition strategies of Malassezia and lays the foundation for future research on the role of siderophore transporters in this skin-associated fungus.