Pathogenomic analysis of Lichtheimia species as a model for basal human pathogens of the order Mucorales

Despite the increasing recognition of life-threatening infections with members of the Mucorales (mucormycosis), little is known about genomics and the molecular basis of pathogenicity in these fungi. More than 20 mucoralean species are known to cause infections in humans. Although these species are only distantly related, all infections are described by the term mucormycosis and species-specific features are only rarely discussed. Moreover, research on virulence factors is mainly limited to the two derived mucoralean genera Rhizopus and Mucor. Lichtheimia species are basal mucoralean pathogens and represent the second most common cause of mucormycosis in Europe. This work focused on species of the genus Lichtheimia as novel model organisms to study human pathogenic mucoralean fungi. A combination of genomic and transcriptomic approaches was used to get first insights into general genomic features of Lichtheimia as one of the most basal human pathogenic genera among mucoralean fungi and to identify putative virulence factors. In addition, the response of human pathogenic and non-pathogenic Lichtheimia species to infection-associated stress conditions was analysed to investigate the evolution of pathogenicity in these fungi. The comprehensive genome and transcriptome data produced during this study give first insights into the stress response of basal fungi and reveal severe differences compared to other fungi. These data represent a valuable resource for future research and will help to identify virulence factors as well as targets for new antifungals.