Talaromyces marneffei (Penicillium marneffei) is an important fungal pathogen of humans, in particular those who are immunocompromised. T. marneffei has the capacity to alternate between a hyphal and a yeast growth form, a process known as dimorphic switching. The strongest extrinsic trigger for dimorphic switching is in response to temperature. T. marneffei grows in the hyphal form at 25°C and in the yeast form at 37°C. The hyphal form produces conidia that are likely to be the infectious agent and believed to establish infection after inhalation. The yeast growth form is the pathogenic form found in infected patients. These yeast cells exist intracellularly in the mononuclear phagocyte system of the host. The aim of this work is to understand the mechanisms for specifying cell type and to understand how these impact on pathogenicity.
High throughput transcriptomic and metabolomic analyses identified hyphal and yeast cell specific pathways during growth of T. marneffei. Coupled with genomics studies we characterised a number of candidates that were predicted to play a role during growth in the host. One mechanism appears to be major expansions of a number of gene families including genes encoding aspartyl proteases. We showed that this expanded family has important roles whilst T. marneffei is growing inside host cells. We also identified a number of genes that play critical role in yeast cell morphogenesis inside host cells. Cell shape is critical for T. marneffei to survive within host cells without prematurely killing them. The results suggest that T. marneffei has evolved a unique set of strategies to establish and maintain its morphological state in the host and to assimilate nutrients for growth, both of which are central to pathogenicity.