Joseph Lykins, Matthew J Moschitto, Ying Zhou, Ekaterina V Filippova, Hoang V Le, Tadakimi Tomita, Barbara A Fox, David J Bzik, Chunlei Su, Seesandra V Rajagopala, Kristin Flores, Furio Spano, Stuart Woods, Craig W Roberts, Cong Hua, Kamal El Bissati, Kelsey M Wheeler, Sarah Dovgin, Stephen P Muench, Martin McPhillie, Colin W G Fishwick, Wayne F Anderson, Patricia J Lee, Mark Hickman, Louis M Weiss, Jitender P Dubey, Hernan A Lorenzi, Richard B Silverman, Rima L McLeod
Toxoplasma gondii causes morbidity, mortality, and disseminates widely via cat sexual stages. Here, we find T. gondii ornithine aminotransferase (OAT) is conserved across phyla. We solve Tg O/GABA-AT structures with bound inactivators at 1.55 Å and identify an inactivator selective for Tg O/GABA-AT over human OAT and GABA-AT. However, abrogating Tg O/GABA-AT genetically does not diminish replication, virulence, cyst-formation, or eliminate cat's oocyst shedding. Increased sporozoite/merozoite Tg O/GABA-AT expression led to our study of a mutagenized clone with oocyst formation blocked, arresting after forming male and female gametes, with "Rosetta stone"-like mutations in genes expressed in merozoites...
January 19, 2024: IScience