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By Aqsa Raja, Biological Sciences
Advisor: Yoshi Odaka
Presentation ID: 124
Abstract: Naegleria fowleri is a pathogenic unicellular protist of free-living amoeba commonly found in warm freshwater and undergoes three stages of the life cycle, amebic trophozoite, flagellate, and metabolically dormant cyst, depending on the environmental conditions. However, the trophozoite is the only form that invades the central nervous tissues through the nasal cavity and causes highly fatal primary amebic meningoencephalitis (PAM). In this study, the non-pathogenic species, Naegleria gruberi (NEG-M strain, ATCC 30224), was assessed its sensitivities to Streptomyces-derived macrolides rapamycin and FK506, and the ATP-competitive TOR (target of rapamycin) inhibitor, Torin-1. Although expressing the common macrolide receptor, FKBP12, N. gruberi was resistant to the allosteric inhibitors for TOR kinase (rapamycin) and calcineurin phosphatase (FK506) in terms of its viability and locomotion, while showing the vulnerability to Torin-1 in a dose-dependent manner (IC50 = 7.79 nM). Moreover, Torin-1 treatment induced the formation of cyst-like structure and greatly affected ameba's locomotion, suggesting TOR's potential regulatory role in the morphological differentiation and actin filament polymerization in the Naegleria genus.