{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T23:59:38Z","timestamp":1792886378217,"version":"4.5.0"},"posted":{"date-parts":[[2025,12,8]]},"group-title":"Microbiology","reference-count":106,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R35GM138381"],"award-info":[{"award-number":["R35GM138381"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"crossref","award":["I-2075-20240404"],"award-info":[{"award-number":["I-2075-20240404"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Foundation","doi-asserted-by":"crossref","award":["G-1021959"],"award-info":[{"award-number":["G-1021959"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Reactive nitrogen species (RNS) are a mechanism to control microbial infections conserved across the host species of the obligate intracellular parasite\n                  <jats:italic>Toxoplasma gondii.<\/jats:italic>\n                  Cysteine S-nitrosylation (SNO) is a reversible post-translational modification that controls complex cell behaviors by regulating protein interactions and signal transduction events. Here we identified a cluster of\n                  <jats:italic>T. gondii<\/jats:italic>\n                  secreted effector proteins that are SNO-modified in a host inducible nitric oxide synthetase (iNOS)-dependent manner. Among these were the rhoptry protein 5 (ROP5) paralogs, which are the major virulence determinants in\n                  <jats:italic>T. gondii<\/jats:italic>\n                  and an immunodominant antigen in B6 mice. ROP5 was necessary for Type I and Type II parasites to evade IFN-\u03b3-mediated immune clearance in iNOS-deficient macrophages. RNS led to the loss of ROP5 association with the parasitophorous vacuole membrane, which is necessary for the known functions of ROP5. Infection with ROP5 knockout parasites rescued the susceptibility of iNOS-deficient mice to infection with Type II\n                  <jats:italic>T. gondii.<\/jats:italic>\n                  Together, these data indicate that RNS can promote cell-autonomous parasite clearance by inhibiting the function of ROP5 paralogs at the parasitophorous vacuole membrane.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Importance<\/jats:title>\n                  <jats:p>\n                    RNS are necessary for cell-autonomous immunity to\n                    <jats:italic>T. gondii<\/jats:italic>\n                    infection; however, the molecular mechanisms by which RNS regulate parasite control remain poorly understood. Our findings support a model where post-translational modification of ROP5 by RNS is a conserved mechanism of inhibiting the functions of divergent ROP5 paralogs. These data provide a specific example of how host RNS are used to counter\n                    <jats:italic>T. gondii<\/jats:italic>\n                    immune evasion effectors that can be applied to understand how nitrosylation regulates the function of other parasite effectors and the role of RNS in the control of other intracellular pathogens.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2025.12.08.693015","type":"posted-content","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T07:10:14Z","timestamp":1765264214000},"source":"Crossref","is-referenced-by-count":3,"title":["Cysteine-S-nitrosylation inhibits Rop5-mediated immune evasion in\n                  <i>Toxoplasma gondii<\/i>"],"prefix":"10.64898","author":[{"given":"SL","family":"Lempke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PC","family":"DiMare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Nichols","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"AM","family":"Chaudry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LF","family":"Fitzsimmons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9401-9594","authenticated-orcid":false,"given":"ML","family":"Reese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5327-7578","authenticated-orcid":false,"given":"SE","family":"Ewald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025121106350549000_2025.12.08.693015v1.1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/126.6.664"},{"key":"2025121106350549000_2025.12.08.693015v1.2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/154.4.357"},{"key":"2025121106350549000_2025.12.08.693015v1.3","doi-asserted-by":"crossref","first-page":"12616","DOI":"10.1038\/s41598-024-63263-w","article-title":"Optimal control strategies for toxoplasmosis disease transmission dynamics via harmonic mean-type incident rate","volume":"14","year":"2024","journal-title":"Sci Rep"},{"key":"2025121106350549000_2025.12.08.693015v1.4","doi-asserted-by":"crossref","first-page":"e0290769","DOI":"10.1371\/journal.pone.0290769","article-title":"The epidemiology of patients with toxoplasmosis and its associated risk factors in Taiwan during the 2007-2020 period","volume":"18","year":"2023","journal-title":"PLoS One"},{"key":"2025121106350549000_2025.12.08.693015v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2020.11.001"},{"key":"2025121106350549000_2025.12.08.693015v1.6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.62.081307.162925"},{"key":"2025121106350549000_2025.12.08.693015v1.7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1015338108"},{"key":"2025121106350549000_2025.12.08.693015v1.8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005434"},{"key":"2025121106350549000_2025.12.08.693015v1.9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.253435"},{"key":"2025121106350549000_2025.12.08.693015v1.10","doi-asserted-by":"crossref","unstructured":"Fox BA , Rommereim LM , Guevara RB , Falla A , Hortua Triana MA , Sun Y , Bzik DJ . 2016. 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