Category
Basic
Description
Cryptococcus neoformans is an opportunistic fungal pathogen that causes lethal cryptococcal meningitis in immunocompromised individuals, such as the AIDS community or those who are undergoing cancer treatment. The yeast is responsible for around 19% of all AIDS related deaths annually and has been classified among the highest ranked fungal pathogens on the World Health Organization’s (WHO) Fungal Priority Pathogens List (FPPL). Antifungal resistance has stimulated increasing concern with C. neoformans. The primary route of infection is the inhalation of basidiospores from environmental reservoirs such as bird droppings and tree detritus. Germination of the basidiospores and survival of yeasts within the human body are heavily dependent on pH adaptation. A previous study at Duke University identified various genes potentially involved in pH adaption including GeneID CNAG_02291. This gene, herein designated as DCM1 (DASH Complex with Microtubules) in C. neoformans, shows sequence homology with DAM1 in S. cerevisiae, which is known to be vitally involved in the segregation of chromosomes during mitosis. It is our goal to assess the relationship of the RIM101 and SRE1 pH regulatory pathways on DCM1 expression and virulence. The effects of DCM1 deletion on virulence will be evaluated using the invertebrate model, Galleria mellonella. Additionally, ploidy effects of DCM1 deletion will also be assessed via PI fluorescence with flow cytometry. DCM1’s involvement in the RIM101 and SRE1 pathways will be analyzed utilizing real-time quantitative PCR to measure gene expression. Overall, this research project seeks to expand previous studies and further understanding of the role DCM1 plays in virulence, ploidy, and pH adaption of C. neoformans.
The Putative DASH Complex Gene DCM1 Influences pH Adaptation and Virulence in Cryptococcus neoformans
Basic
Cryptococcus neoformans is an opportunistic fungal pathogen that causes lethal cryptococcal meningitis in immunocompromised individuals, such as the AIDS community or those who are undergoing cancer treatment. The yeast is responsible for around 19% of all AIDS related deaths annually and has been classified among the highest ranked fungal pathogens on the World Health Organization’s (WHO) Fungal Priority Pathogens List (FPPL). Antifungal resistance has stimulated increasing concern with C. neoformans. The primary route of infection is the inhalation of basidiospores from environmental reservoirs such as bird droppings and tree detritus. Germination of the basidiospores and survival of yeasts within the human body are heavily dependent on pH adaptation. A previous study at Duke University identified various genes potentially involved in pH adaption including GeneID CNAG_02291. This gene, herein designated as DCM1 (DASH Complex with Microtubules) in C. neoformans, shows sequence homology with DAM1 in S. cerevisiae, which is known to be vitally involved in the segregation of chromosomes during mitosis. It is our goal to assess the relationship of the RIM101 and SRE1 pH regulatory pathways on DCM1 expression and virulence. The effects of DCM1 deletion on virulence will be evaluated using the invertebrate model, Galleria mellonella. Additionally, ploidy effects of DCM1 deletion will also be assessed via PI fluorescence with flow cytometry. DCM1’s involvement in the RIM101 and SRE1 pathways will be analyzed utilizing real-time quantitative PCR to measure gene expression. Overall, this research project seeks to expand previous studies and further understanding of the role DCM1 plays in virulence, ploidy, and pH adaption of C. neoformans.
