{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:25:10Z","timestamp":1791235510237,"version":"4.1.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"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><jats:italic>Toxoplasma gondii<\/jats:italic> is an obligate intracellular parasite that modulates a broad range of host cell functions to guarantee its intracellular development and replication. <jats:italic>T. gondii<\/jats:italic> includes three classical clonal lineages exhibiting different degrees of virulence. Regarding the genetic diversity of <jats:italic>T. gondii<\/jats:italic> circulating in Europe, type II strains and, to a lesser extent, type III strains are the dominant populations, both in humans and animals. Infections with the type I strain led to widespread parasite dissemination and death in mice, while type III is considered avirulent. Previously, we demonstrated that primary endothelial cells infected with the <jats:italic>T. gondii<\/jats:italic> RH strain (haplotype I) were arrested in the G2\/M-phase transition, triggering cytokinesis failure and chromosome missegregation. Since <jats:italic>T. gondii<\/jats:italic> haplotypes differ in their virulence, we here studied whether <jats:italic>T. gondii<\/jats:italic>-driven host cell cycle perturbation is strain-dependent. Primary endothelial cells were infected with <jats:italic>T. gondii<\/jats:italic> Me49 (type II strain) or NED (type III strain), and their growth kinetics were compared up to cell lysis (6\u201330\u2009h p. i.). In this study, only slight differences in the onset of full proliferation were observed, and developmental data in principle matched those of the RH strain. FACS-based DNA quantification to estimate cell proportions experiencing different cell cycle phases (G0\/1-, S-, and G2\/M-phase) revealed that Me49 and NED strains both arrested the host cell cycle in the S-phase. Cyclins A2 and B1 as key molecules of S- and M-phase were not changed by Me49 infection, while NED infection induced cyclin B1 upregulation. To analyze parasite-driven alterations during mitosis, we demonstrated that both Me49 and NED infections led to impaired host cellular chromosome segregation and irregular centriole overduplication. Moreover, in line with the RH strain, both strains boosted the proportion of binucleated cells within infected endothelial cell layers, thereby indicating enhanced cytokinesis failure. Taken together, we demonstrate that all parasite-driven host cell cycle arrest, chromosome missegregation, and binucleated phenotypes are <jats:italic>T. gondii<\/jats:italic>-specific but strain independent.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1336267","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T05:44:26Z","timestamp":1708494266000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Toxoplasma gondii Me49 and NED strains arrest host cell cycle progression and alter chromosome segregation in a strain-independent manner"],"prefix":"10.3389","volume":"15","author":[{"given":"Lisbeth","family":"Rojas-Bar\u00f3n","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Hermosilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Taubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahady D.","family":"Vel\u00e1squez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1152\/physrev.00032.2006","article-title":"Cardiac myocyte cell cycle control in development, disease, and regeneration","volume":"87","author":"Ahuja","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref2","doi-asserted-by":"crossref","DOI":"10.1201\/9780203833445-17","article-title":"The cell cycle","volume-title":"Molecular biology of the cell 5th edition, Garland Science,","author":"Alberts","year":"2007"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1111\/j.1462-5822.2007.01093.x","article-title":"Toxoplasma gondii exploits UHRF1 and induces host cell cycle arrest at G2 to enable its proliferation","volume":"10","author":"Brunet","year":"2008","journal-title":"Cell. Microbiol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"868727","DOI":"10.3389\/fcimb.2022.868727","article-title":"Unifying virulence evaluation in Toxoplasma gondii: a timely task","volume":"12","author":"Calero-Bernal","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e111297","DOI":"10.1371\/journal.pone.0111297","article-title":"Distinct strains of Toxoplasma gondii feature divergent transcriptomes regardless of developmental stage","volume":"9","author":"Croken","year":"2014","journal-title":"PLoS One"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/B978-0-12-396481-6.00003-9","article-title":"Chapter 3 - molecular epidemiology and population structure of Toxoplasma gondii","volume-title":"Toxoplasma gondii","author":"Dard\u00e9","year":"2014"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s13567-021-00953-7","article-title":"In vivo and in vitro models show unexpected degrees of virulence among Toxoplasma gondii type II and III isolates from sheep","volume":"52","author":"Fern\u00e1ndez-Escobar","year":"2021","journal-title":"Vet. Res."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"842595","DOI":"10.3389\/fcimb.2022.842595","article-title":"Toxoplasma gondii genotyping: a closer look into Europe","volume":"12","author":"Fern\u00e1ndez-Escobar","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1083\/jcb.201210040","article-title":"Linking abnormal mitosis to the acquisition of DNA damage","volume":"199","author":"Ganem","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1016\/j.ijpara.2008.06.004","article-title":"The cell cycle and Toxoplasma gondii cell division: tightly knit or loosely stitched?","volume":"38","author":"Gubbels","year":"2008","journal-title":"Int. J. Parasitol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1093\/infdis\/172.6.1561","article-title":"Toxoplasma gondii comprises three clonal lineages: correlation of parasite genotype with human disease","volume":"172","author":"Howe","year":"1995","journal-title":"J. Infect. Dis."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"14872","DOI":"10.1073\/pnas.0702356104","article-title":"Recent transcontinental sweep of Toxoplasma gondii driven by a single monomorphic chromosome","volume":"104","author":"Khan","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"147","DOI":"10.3347\/kjp.2016.54.2.147","article-title":"Exosomes secreted by Toxoplasma gondii-infected L6 cells: their effects on host cell proliferation and cell cycle changes","volume":"54","author":"Kim","year":"2016","journal-title":"Korean J. Parasitol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"3607","DOI":"10.1242\/jcs.114.20.3607","article-title":"Steps of nuclear pore complex disassembly and reassembly during mitosis in early Drosophila embryos","volume":"114","author":"Kiseleva","year":"2001","journal-title":"J. Cell Sci."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.molcel.2004.07.012","article-title":"Mitotic spindle assembly and chromosome segregation: refocusing on microtubule dynamics","volume":"15","author":"Kline-Smith","year":"2004","journal-title":"Mol. Cell"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1101\/gad.314351.118","article-title":"The impact of mitotic errors on cell proliferation and tumorigenesis","volume":"32","author":"Levine","year":"2018","journal-title":"Genes Dev."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"3164","DOI":"10.1182\/blood-2008-03-144956","article-title":"Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and rho\/rock signaling","volume":"112","author":"Lordier","year":"2008","journal-title":"Blood"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"10147","DOI":"10.1038\/ncomms10147","article-title":"Local admixture of amplified and diversified secreted pathogenesis determinants shapes mosaic Toxoplasma gondii genomes","volume":"7","author":"Lorenzi","year":"2016","journal-title":"Nat. Commun."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"R688","DOI":"10.1016\/j.cub.2018.05.019","article-title":"Cohesin and chromosome segregation","volume":"28","author":"Makrantoni","year":"2018","journal-title":"Curr. Biol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"3633","DOI":"10.1242\/jcs.016907","article-title":"Liver tetraploidization is controlled by a new process of incomplete cytokinesis","volume":"120","author":"Margall-Ducos","year":"2007","journal-title":"J. Cell Sci."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1586\/14789450.2.5.719","article-title":"Histone structure and nucleosome stability","volume":"2","author":"Mari\u00f1o-Ram\u00edrez","year":"2005","journal-title":"Expert Rev. Proteomics"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e44700","DOI":"10.7554\/eLife.44700","article-title":"Mammalian cell growth dynamics in mitosis","volume":"8","author":"Miettinen","year":"2019","journal-title":"eLife"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1116899","DOI":"10.3389\/fmars.2023.1116899","article-title":"Newly detected, virulent Toxoplasma gondii COUG strain causing fatal steatitis and toxoplasmosis in southern sea otters (Enhydra lutris nereis)","volume":"10","author":"Miller","year":"2023","journal-title":"Front. Mar. Sci."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1111\/j.1462-5822.2008.01117.x","article-title":"Infection with Toxoplasma gondii results in dysregulation of the host cell cycle","volume":"10","author":"Molestina","year":"2008","journal-title":"Cell. Microbiol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1083\/jcb.139.2.449","article-title":"Thrombopoietin-induced polyploidization of bone marrow megakaryocytes is due to a unique regulatory mechanism in late mitosis","volume":"139","author":"Nagata","year":"1997","journal-title":"J. Cell Biol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e0147420","DOI":"10.1371\/journal.pone.0147420","article-title":"Chromosome bridges maintain kinetochore-microtubule attachment throughout mitosis and rarely break during anaphase","volume":"11","author":"Pampalona","year":"2016","journal-title":"PLoS One"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e0016022","DOI":"10.1128\/msphere.00160-22","article-title":"Disruption of Toxoplasma gondii-induced host cell DNA replication is dependent on contact inhibition and host cell type","volume":"7","author":"Pierre-Louis","year":"2022","journal-title":"mSphere"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1146\/annurev.cb.09.110193.000435","article-title":"Functional elements of the cytoskeleton in the early Drosophila embryo","volume":"9","author":"Schejter","year":"1993","journal-title":"Annu. Rev. Cell Biol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1038\/359082a0","article-title":"Virulent strains of Toxoplasma gondii comprise a single clonal lineage","volume":"359","author":"Sibley","year":"1992","journal-title":"Nature"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"10753","DOI":"10.1073\/pnas.172117099","article-title":"Identification of quantitative trait loci controlling acute virulence in Toxoplasma gondii","volume":"99","author":"Su","year":"2002","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"12496","DOI":"10.1038\/s41598-019-48961-0","article-title":"Toxoplasma gondii-induced host cellular cell cycle dysregulation is linked to chromosome missegregation and cytokinesis failure in primary endothelial host cells","volume":"9","author":"Vel\u00e1squez","year":"2019","journal-title":"Sci. Rep."},{"key":"ref33","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4939-9857-9_5","article-title":"Assays for monitoring Toxoplasma gondii infectivity in the laboratory mouse","volume-title":"Toxoplasma gondii. Methods in Molecular Biology","author":"Wang","year":"2020"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.pt.2018.07.006","article-title":"Apicomplexa cell cycles: something old, borrowed, lost, and new","volume":"34","author":"White","year":"2018","journal-title":"Trends Parasitol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.ijpara.2020.05.001","article-title":"Cell type- and species-specific host responses to Toxoplasma gondii and its near relatives","volume":"50","author":"Wong","year":"2020","journal-title":"Int. J. Parasitol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/s41541-022-00518-5","article-title":"Live-attenuated ME49\u0394cdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis","volume":"7","author":"Wu","year":"2022","journal-title":"NPJ Vaccines"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1336267\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T05:44:30Z","timestamp":1708494270000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1336267\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,21]]},"references-count":36,"alternative-id":["10.3389\/fmicb.2024.1336267"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2024.1336267","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,21]]},"article-number":"1336267"}}