This week we profile a recent publication in PLOS Pathogens from
Dr. James Kronstad (back, middle) at the Michael Smith Laboratories.
Can you provide a brief overview of your lab’s current research focus?
The research program in the Kronstad laboratory focuses on identifying the molecular mechanisms required for disease development by the pathogenic fungus Cryptococcus neoformans. C. neoformans is a causative agent of cryptococcal meningitis, a disease that is estimated to cause ~ 15% of AIDS-related deaths. In this context, cryptococosis is one of the most common cause of mortality in people with HIV/AIDS, closely behind tuberculosis. Unfortunately, very few antifungal drugs are available to treat cryptococcal meningitis. The studies in the Kronstad laboratory are based on the premise that understanding mechanisms of pathogenesis for C. neoformans will lead to new therapeutic avenues. We are particularly interested in mechanisms of iron homeostasis because the battle for iron between invading microorganisms and mammalian hosts is a pivotal determinant of the outcome of infection.
What is the significance of the findings in this publication?
This study provides new insights into the machinery that mediates uptake of iron as an essential nutrient, as well as mechanisms of trafficking of iron between organelles; it also establishes the relevance of endocytosis in the pathogenicity of C. neoformans. Specifically, we found that the Vps45 protein, which regulates vesicle fusion, participates in the trafficking of iron into fungal cells, supports mitochondria function, mediates antifungal resistance and is required for virulence. These discoveries provide new targets for potentially interfering with the virulence of C. neoformans because they shed light on the molecular mechanisms underlying the uptake and use of iron as an essential nutrient.
What are the next steps for this research?
Many questions remain regarding the roles of additional trafficking components and the mechanisms of delivery to target organelles, particularly in the context of iron and heme delivery to mitochondria. Further investigation could lead to the identification of key targets for iron use and the development of drugs that target Vps45-mediated processes.
This research was funded by:
This work was supported by grants from the Canadian Institutes of Health Research (MOP13234, to JWK), the National Institutes of Health (RO1AI053721, to JWK) and the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT and Future Planning (NRF-2016R1D1A1B03931890, to WHJ).
