{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:26:58Z","timestamp":1792132018957,"version":"4.4.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T00:00:00Z","timestamp":1709856000000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:p><jats:italic>Toxoplasma gondii<\/jats:italic> is a globally occurring apicomplexan parasite that infects humans and animals. Globally, different typical and atypical haplotypes of <jats:italic>T. gondii<\/jats:italic> induce varying pathologies in hosts. As an obligate intracellular protozoon, <jats:italic>T. gondii<\/jats:italic> was shown to interfere with host cell cycle progression, leading to mitotic spindle alteration, chromosome segregation errors and cytokinesis failure which all may reflect chromosomal instability. Referring to strain-dependent virulence, we here studied the potential of different <jats:italic>T. gondii<\/jats:italic> strains (RH, Me49 and NED) to drive DNA damage in primary endothelial host cells. Utilizing microscopic analyses, comet assays and \u03b3-H2AX quantification, we demonstrated a strain-dependent induction of binucleated host cells, DNA damage and DNA double strand breaks, respectively, in <jats:italic>T. gondii<\/jats:italic>-infected cells with the RH strain driving the most prominent effects. Interestingly, only the NED strain significantly triggered micronuclei formation in <jats:italic>T. gondii<\/jats:italic>-infected cells. Focusing on the RH strain, we furthermore demonstrated that <jats:italic>T. gondii<\/jats:italic>-infected primary host cells showed a DNA damage response by activating the ATM-dependent homologous recombination (HR) pathway. In contrast, key molecules of the nonhomologous DNA end joining (NHEJ) pathway were either not affected or downregulated in RH-infected host cells, suggesting that this pathway is not activated by infection. In conclusion, current finding suggests that <jats:italic>T. gondii<\/jats:italic> infection affects the host cell genome integrity in a strain-dependent manner by causing DNA damage and chromosomal instability.<\/jats:p>","DOI":"10.3389\/fcimb.2024.1374659","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T04:32:50Z","timestamp":1709872370000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Toxoplasma gondii infection-induced host cellular DNA damage is strain-dependent and leads to the activation of the ATM-dependent homologous recombination pathway"],"prefix":"10.3389","volume":"14","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":[[2024,3,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1016\/j.cell.2018.08.027","article-title":"The multifaceted role of chromosomal instability in cancer and its microenvironment","volume":"174","author":"Bakhoum","year":"2018","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"12102","DOI":"10.1038\/s41598-020-69078-9","article-title":"Global, regional, and country seroprevalence of Toxoplasma gondii in pregnant women: a systematic review, modelling and meta-analysis","volume":"10","author":"Bigna","year":"2020","journal-title":"Sci. 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