Category
Poster - Basic
Description
Cryptococcus neoformans is the highest ranked pathogen on the Fungal Priority Pathogen List (WHO). Cryptococcal disease begins as pneumonia, crosses the blood-brain barrier, and develops into meningoencephalitis with a 41-61% mortality rate. While most commonly contracted by immunocompromised individuals, infections in immunocompetent individuals do occur. Treatments often produce severe side effects and increased resistance is a developing concern. Our research aims to identify a gene that can be targeted for more effective antifungal therapies. The SCP1 gene is involved in pH regulation and virulence in C. neoformans. Our research hypothesiszes that the SCP1 gene is crucial for the adaptation of this pathogen to its host environment, which changes dramatically from acidic to alkaline. Without this gene C. neoformans cannot adapt to the host environment, and therefore cannot become virulent. We deleted SCP1 from a wildtype strain and evaluated mutant and wildtype for altered growth phenotypes. The mutant strain, scp1∆, displayed growth inhibition at pH8, 1.5M NaCl2, and 7mM CoCl2, supporting our hypothesis. We then reintroduced the SCP1 gene into the mutant strain using biolistic bombardment (i.e. gene gun). The virulence of the three strains (wildtype, mutant, and reconstituted) were analyzed in an invertebrate Galleria moth larvae model. The results support our hypothesis by displaying virulence in the wildtype and reconstituted strains that possess SCP1, while the mutant strain that lacks SCP1 was less virulent. This demonstrates a dependency on the SCP1 gene for survival and virulence. Future research will reevaluate growth phenotypes, compare virulence in a murine model, identify the SCP1 pH response pathway through qPCR, and evaluate antifungal sensitivity to drugs like fluconazole. If the SCP1 gene is responsible for survival and virulence of cryptococcal disease then it can be targeted to develop antifungal therapies more effective then current treatments.
Influence of SCP1 on Cryptococcus neoformans Virulence
Poster - Basic
Cryptococcus neoformans is the highest ranked pathogen on the Fungal Priority Pathogen List (WHO). Cryptococcal disease begins as pneumonia, crosses the blood-brain barrier, and develops into meningoencephalitis with a 41-61% mortality rate. While most commonly contracted by immunocompromised individuals, infections in immunocompetent individuals do occur. Treatments often produce severe side effects and increased resistance is a developing concern. Our research aims to identify a gene that can be targeted for more effective antifungal therapies. The SCP1 gene is involved in pH regulation and virulence in C. neoformans. Our research hypothesiszes that the SCP1 gene is crucial for the adaptation of this pathogen to its host environment, which changes dramatically from acidic to alkaline. Without this gene C. neoformans cannot adapt to the host environment, and therefore cannot become virulent. We deleted SCP1 from a wildtype strain and evaluated mutant and wildtype for altered growth phenotypes. The mutant strain, scp1∆, displayed growth inhibition at pH8, 1.5M NaCl2, and 7mM CoCl2, supporting our hypothesis. We then reintroduced the SCP1 gene into the mutant strain using biolistic bombardment (i.e. gene gun). The virulence of the three strains (wildtype, mutant, and reconstituted) were analyzed in an invertebrate Galleria moth larvae model. The results support our hypothesis by displaying virulence in the wildtype and reconstituted strains that possess SCP1, while the mutant strain that lacks SCP1 was less virulent. This demonstrates a dependency on the SCP1 gene for survival and virulence. Future research will reevaluate growth phenotypes, compare virulence in a murine model, identify the SCP1 pH response pathway through qPCR, and evaluate antifungal sensitivity to drugs like fluconazole. If the SCP1 gene is responsible for survival and virulence of cryptococcal disease then it can be targeted to develop antifungal therapies more effective then current treatments.
Comments
Undergraduate - 1st Place Award Winner