Metabolic reconstruction of five Malassezia genomes

Abstract

Malassezia species, are lipophilic and lipid dependent, belonging to the human and animal microbiota. Usually, they are isolated from regions rich in sebaceous glands. In some individuals they have been associated with different dermatological diseases such as seborrheic dermatitis, tinea versicolor, atopic dermatitis, and folliculitis. Their lipid dependency has been a subject of study mainly due to the fact that the genome sequencing of Malassezia globosa and Malassezia sympodialis, showed the absence of genes related to the synthesis of fatty acids. However, the genome sequence of Malassezia pachydermatis, the only lipid-independent species also shows the absence of fatty acid synthases. The metabolic differences that lead to these diverse phenotypes and their role in adaptation are still unknown. Reconstruction of metabolic networks, based on genome data and its further modeling using COBRA (COnstraints Based Reconstruction and Analysis) based models were performed to elucidate the metabolic differences that may contribute to the phenotypic variations that occur in this genus and the possible relation with virulence. The goal of this study was to investigate the metabolic behavior of Malassezia by obtaining a metabolic reconstruction and highlighting the similarities and differences among the lipid synthesis pathways of five Malassezia species. The metabolic reconstruction was then modeled using constrained models of the five Malassezia species predicting an interesting variation in the fluxes of each reaction over the network to satisfy the biomass objective function. This suggests several possible mechanisms involving steroid, butanoate metabolism among others that might explain the yeast growth in different lipidic conditions. We further identified diverse lipid pathways and enzymes that could have a role in the pathogenesis of these yeasts.