Determining the role of 14-3-3 protein in regulating intracellular growth of the human pathogen Cryptococcus

Abstract

Cryptococcus spp. cause invasive fungal infections, which are responsible for high rates of morbidity and mortality. The fungus can transfer among macrophages by both lytic and non-lytic methods, facilitating dissemination within the host organism. Previous studies have identified a key role for cryptococcal extracellular vesicles (EVs) in regulating the proliferation of this fungus within the host. The 14-3-3 protein is abundant in cryptococcal EVs and has been previously implicated in pathogenesis in other fungi. However, how 14-3-3 protein regulates cryptococcal virulence, and whether this is via an EV-mediated mechanism, remains unknown. Thus, the aim of this project is to analyze the role of 14-3-3 protein in the two major pathogenic species of Cryptococcus (C. neoformans and C. gattii) by combining genetic and pharmacological inhibition with in vitro infection assays and high-resolution imaging techniques.