| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 27, Iss 1, Pp 108477- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2023.108477 |
| Popis: |
Summary: 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 TgO/GABA-AT structures with bound inactivators at 1.55 Å and identify an inactivator selective for TgO/GABA-AT over human OAT and GABA-AT. However, abrogating TgO/GABA-AT genetically does not diminish replication, virulence, cyst-formation, or eliminate cat’s oocyst shedding. Increased sporozoite/merozoite TgO/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. Mutations are similar to those in organisms from plants to mammals, causing defects in conception and zygote formation, affecting merozoite capacitation, pH/ionicity/sodium-GABA concentrations, drawing attention to cyclic AMP/PKA, and genes enhancing energy or substrate formation in TgO/GABA-AT-related-pathways. These candidates potentially influence merozoite’s capacity to make gametes that fuse to become zygotes, thereby contaminating environments and causing disease. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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