Abstract
Cryptococcus gattii is a basidiomycetous yeast that can be found in the environment and is one of the agents of cryptococcosis, a life-threatening disease. During its life cycle, cryptococcal cells take hold inside environmental predators such as amoebae. Despite their evolutionary distance, macrophages and amoebae share conserved similar steps of phagocytosis and microbial killing. To evaluate whether amoebae also share other antifungal strategies developed by macrophages, we investigated nutritional immunity against cryptococcal cells. We focused on zinc homeostasis modulation in Acanthamoeba castellanii infected with C. gattii. The intracellular proliferation rate (IPR) in amoebae was determined using C. gattii R265 and mutants for the ZIP1 gene, which displays defects of growth in zinc-limiting conditions. We detected a reduced IPR in cells lacking the ZIP1 gene compared to wild-type strains, suggesting that amoebae produce a low zinc environment to engulfed cells. Furthermore, flow cytometry analysis employing the zinc probe Zinpyr-1 confirmed the reduced concentration of zinc in cryptococcal-infected amoebae. qRT-PCR analysis of zinc transporter-coding genes suggests that zinc export by members of the ZnT family would be involved in the reduced intracellular zinc concentration. These results indicate that amoebae may use nutritional immunity to reduce fungal cell proliferation by reducing zinc availability for the pathogen.
Highlights
Cryptococcus gattii and Cryptococcus neoformans are basidiomycetous yeasts that can be found in the environment and are the etiological agents of cryptococcosis, a life-threatening disease that is associated with nearly 200,000 annual deaths worldwide (Rajasingham et al, 2017)
We found that A. castellanii cells actively reduced zinc levels after exposure to C. gattii, possibly by mechanisms that include the activity of zinc exporters belonging to the ZnT family
Zinc Uptake Is Important for C. gattii Survival in A. castellanii
Summary
Cryptococcus gattii and Cryptococcus neoformans are basidiomycetous yeasts that can be found in the environment and are the etiological agents of cryptococcosis, a life-threatening disease that is associated with nearly 200,000 annual deaths worldwide (Rajasingham et al, 2017). Infection in mammalian hosts is initiated by the inhalation of airborne dehydrated yeast cells or spores that reach the lung and typically cause pneumonia or meningitis, which are driven by dissemination through the blood system (Harris et al, 2013). Alveolar macrophages initiate host defense by phagocytosis of the yeast cells. The best-characterized virulence factors in cryptococcal species include the production of a polysaccharide capsule, the synthesis of melanin and the secretion of enzymes that can destroy host cells. The production of such virulence factors allows cryptococcal survival in host cells and fluids (Coelho et al, 2014)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
