Science Bite (3 min Oral Presentation) Lorne Infection and Immunity 2019

Identifying the transcriptional response of the opportunistic, dimorphic human pathogen Talaromyces marneffei to growth within macrophages (#52)

Harshini Weerasinghe 1 , Alex Andrianopoulos 1 , Hayley E Bugeja 1
  1. The University of Melbourne, Parkville, VIC, Australia

Fungal pathogens of animals and plants are a major concern with huge economic and public health consequences. The emergence of opportunistic fungal pathogens that cause human disease exacerbates the current problem. It is therefore essential to understand the mechanisms that fungi employ to survive within a host. Talaromyces marneffei is a dimorphic, opportunistic pathogenic fungus that infects immunocompromised individuals. T. marneffei grows as a multicellular hyphal form at 25°C, capable of producing infectious conidia, which upon inhalation reach the alveoli of the lungs where they are phagocytosed by resident phagocytes such as alveolar macrophages. The transition to 37°C, which is the human host body temperature, induces the dimorphic switch to a pathogenic, uninucleate, fission yeast form. The yeast form is able to use macrophages as a niche to avoid immune detection, acquire nutrients and withstanding macrophage-killing mechanisms. To determine the transcriptional response of T. marneffei to the host environment, including those induced by growth at body temperature and host-derived cellular signals, ChIPseq and RNAseq analysis was used to create a profile of T. marneffei gene expression during in vitro growth and during murine and human macrophage infection. Key nutritional and cell protective pathways that show common upregulation during the yeast growth phase were identified and these included carbon and nitrogen utilization, micronutrient uptake, melanin generation and oxidative stress protection. Additionally, several host responsive genes important for establishing viability and morphological maintenance of T. marneffei yeast growth in macrophages were identified and functionally validated. These findings revealed that T. marneffei has adapted specific temperature and/or host responsive programs tailored to the diverse environmental conditions encountered by hyphal and yeast morphological forms.