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Avirulent Uracil Auxotrophs Based On Disruption Of Orotidine-5′-Monophosphate Decarboxylase Elicit Protective Immunity To Toxoplasma Gondii, Barbara A. Fox, David J. Bzik
Avirulent Uracil Auxotrophs Based On Disruption Of Orotidine-5′-Monophosphate Decarboxylase Elicit Protective Immunity To Toxoplasma Gondii, Barbara A. Fox, David J. Bzik
Dartmouth Scholarship
The orotidine-5'-monophosphate decarboxylase (OMPDC) gene, encoding the final enzyme of the de novo pyrimidine biosynthesis pathway, was deleted using Toxoplasma gondii KU80 knockouts to develop an avirulent nonreverting pyrimidine auxotroph strain. Additionally, to functionally address the role of the pyrimidine salvage pathway, the uridine phosphorylase (UP) salvage activity was knocked out and a double knockout of UP and OMPDC was also constructed. The nonreverting DeltaOMPDC, DeltaUP, and DeltaOMPDC DeltaUP knockout strains were evaluated for pyrimidine auxotrophy, for attenuation of virulence, and for their ability to elicit potent immunity to reinfection. The DeltaUP knockout strain was replication competent and virulent. In …