Program Book - 27th Fungal Genetics Conference

CONCURRENT SESSION ABSTRACTSGenes important for in vivo survival of the human pathogen Penicillium marneffei. Harshini C. Weerasinghe, Michael J. Payne, Hayley E. Bugeja, AlexAndrianopoulos. Genetics, The University of Melbourne, Parkville, Victoria, Australia.Pathogenic fungi are having an increasing global impact in the areas of health, agriculture and the environment. As such it is essential to understand themechanisms that fungi employ to survive and grow within a host. The emergence of many new “opportunistic fungal pathogens” has to a great extentaltered the traditional view that pathogenicity was solely reliant on the inherent properties of the pathogen. In fact, the ability of a pathogen to causedisease in some hosts but not in others suggests that pathogenic determinants are complex and dynamic, and are largely dependent on specific pathogenhostrelationships. Despite this there are conserved aspects of the interactions between host and pathogen. For example., hosts employ innate immuneresponses as an almost immediate recognition and attack mechanism against invading pathogens. Penicillium marneffei is a temperature dependentdimorphic fungus, growing in a hyphal form producing conidia at 25°C and as a yeast form at 37°C. Despite its importance as an opportunistic pathogen,little is known about the biology and mechanism of infection of P. marneffei. The infectious agents (conidia) are believed to be inhaled, reaching thealveoli of the lungs, where they are phagocytosed by alveolar macrophages for elimination. At this point that P. marneffei switches growth to a pathogenicyeast cell form, and is able to withstand macrophage cytotoxic attacks to cause infection. In order to understand how P. marneffei responds to the host,RNA-seq analysis was used to create a transcriptomic profile of P. marneffei, when infected in murine macrophages. These results were compared to RNAseqdata from hyphal (25°C) and yeast (37°C) cells grown in vitro in order to identify genes that are specifically upregulated during infection. Based on thisanalysis a group of genes of varying functions were chosen for gene deletion studies and tested for defects in pathogenicity. Among these is a group ofPep1-like aspartic endopeptidases which are a uniquely expanded family in P. marneffei and that show reduced virulence in a macrophage model.86