{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T20:12:40Z","timestamp":1788466360822,"version":"build-2803163510"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T00:00:00Z","timestamp":1700697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Serine\/arginine-rich (SR) proteins are key factors with important roles in constitutive and alternative splicing (AS) of pre-mRNAs. However, the role of SR splicing factors in the pathogenicity of <jats:italic>T. gondii<\/jats:italic> remains largely unexplored. Here, we investigated the role of splicing factor SR2, a homolog of <jats:italic>Plasmodium falciparum<\/jats:italic> SR1, in the pathogenicity of <jats:italic>T. gondii<\/jats:italic>. We functionally characterized the predicted SR2 in <jats:italic>T. gondii<\/jats:italic> by gene knockout and studied its subcellular localization by endogenous protein HA tagging using CRISPR-Cas9 gene editing. The results showed that SR2 was localized in the nucleus and expressed in the tachyzoite and bradyzoite stages. <jats:italic>In vitro<\/jats:italic> studies including plaque formation, invasion, intracellular replication, egress and bradyzoite differentiation assays showed that deletion of SR2 in type I RH strain and type II Pru strains had no significant effect on the parasite growth and bradyzoite differentiation (<jats:italic>p<\/jats:italic> &amp;gt;\u20090.05). Interestingly, the disruption of SR2 in RH type I (<jats:italic>p<\/jats:italic> &amp;lt;\u20090.0001) and Pru type II (<jats:italic>p<\/jats:italic> &amp;lt;\u20090.05) strains resulted in varying degrees of attenuated virulence. In addition, disruption of SR2 in type II Pru strain significantly reduced brain cyst burden by ~80% (<jats:italic>p<\/jats:italic> &amp;lt;\u20090.0001). Collectively, these results suggest that splicing factor SR2 is important for the pathogenicity of <jats:italic>T. gondii<\/jats:italic>, providing a new target for the control and treatment of toxoplasmosis.<\/jats:p>","DOI":"10.3389\/fmicb.2023.1302512","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T11:49:37Z","timestamp":1700740177000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["The splicing factor SR2 is an important virulence factor of Toxoplasma gondii"],"prefix":"10.3389","volume":"14","author":[{"given":"Xiao-Jing","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Nan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hany M.","family":"Elsheikha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Ting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Jie","family":"Kou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Quan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1128\/iai.00864-12","article-title":"SR-like RNA-binding protein Slr1 affects Candida albicans filamentation and virulence","volume":"81","author":"Ariyachet","year":"2013","journal-title":"Infect. 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Cell"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.3389\/fimmu.2018.01505","article-title":"Immunization with a DNA vaccine cocktail encoding TgPF, TgROP16, TgROP18, TgMIC6, and TgCDPK3 genes protects mice against chronic toxoplasmosis","volume":"9","author":"Zhang","year":"2018","journal-title":"Front. Immunol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"e0307822","DOI":"10.1128\/spectrum.03078-22","article-title":"Functional characterization of 15 novel dense granule proteins in Toxoplasma gondii using the CRISPR-Cas9 system","volume":"11","author":"Zheng","year":"2023","journal-title":"Microbiol. Spectr."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1302512\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T11:49:40Z","timestamp":1700740180000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1302512\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,23]]},"references-count":39,"alternative-id":["10.3389\/fmicb.2023.1302512"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2023.1302512","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,23]]},"article-number":"1302512"}}