{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T12:02:36Z","timestamp":1778328156662,"version":"3.51.4"},"reference-count":60,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:00:00Z","timestamp":1686873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:00:00Z","timestamp":1686873600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI143707"],"award-info":[{"award-number":["R01AI143707"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI128356"],"award-info":[{"award-number":["R01AI128356"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI096836"],"award-info":[{"award-number":["R01AI096836"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["T32AI060546"],"award-info":[{"award-number":["T32AI060546"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001209","name":"Knights Templar Eye Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001209","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["1P20GM146584-01"],"award-info":[{"award-number":["1P20GM146584-01"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Microbial pathogens use proteases for their infections, such as digestion of proteins for nutrients and activation of their virulence factors. As an obligate intracellular parasite,\n            <jats:italic>Toxoplasma gondii<\/jats:italic>\n            must invade host cells to establish its intracellular propagation. To facilitate invasion, the parasites secrete invasion effectors from microneme and rhoptry, two unique organelles in apicomplexans. Previous work has shown that some micronemal invasion effectors experience a series of proteolytic cleavages within the parasite\u2019s secretion pathway for maturation, such as the aspartyl protease (TgASP3) and the cathepsin L-like protease (TgCPL), localized within the post-Golgi compartment and the endolysosomal system, respectively. Furthermore, it has been shown that the precise maturation of micronemal effectors is critical for\n            <jats:italic>Toxoplasma<\/jats:italic>\n            invasion and egress. Here, we show that an endosome-like compartment (ELC)-residing cathepsin C-like protease (TgCPC1) mediates the final trimming of some micronemal effectors, and its loss further results in defects in the steps of invasion, egress, and migration throughout the parasite\u2019s lytic cycle. Notably, the deletion of TgCPC1 completely blocks the activation of subtilisin-like protease 1 (TgSUB1) in the parasites, which globally impairs the surface-trimming of many key micronemal invasion and egress effectors. Additionally, we found that\n            <jats:italic>Toxoplasma<\/jats:italic>\n            is not efficiently inhibited by the chemical inhibitor targeting the malarial CPC ortholog, suggesting that these cathepsin C-like orthologs are structurally different within the apicomplexan phylum. Collectively, our findings identify a novel function of TgCPC1 in processing micronemal proteins within the\n            <jats:italic>Toxoplasma<\/jats:italic>\n            parasite\u2019s secretory pathway and expand the understanding of the roles of cathepsin C protease.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Toxoplasma gondii<\/jats:italic>\n            is a microbial pathogen that is well adapted for disseminating infections. It can infect virtually all warm-blooded animals. Approximately one-third of the human population carries toxoplasmosis. During infection, the parasites sequentially secrete protein effectors from the microneme, rhoptry, and dense granule, three organelles exclusively found in apicomplexan parasites, to help establish their lytic cycle. Proteolytic cleavage of these secretory proteins is required for the parasite\u2019s optimal function. Previous work has revealed that two proteases residing within the parasite\u2019s secretory pathway cleave micronemal and rhoptry proteins, which mediate parasite invasion and egress. Here, we demonstrate that a cathepsin C-like protease (TgCPC1) is involved in processing several invasion and egress effectors. The genetic deletion of\n            <jats:italic>TgCPC1<\/jats:italic>\n            prevented the complete maturation of some effectors in the parasites. Strikingly, the deletion led to a full inactivation of one surface-anchored protease, which globally impaired the trimming of some key micronemal proteins before secretion. Therefore, this finding represents a novel post-translational mechanism for the processing of virulence factors within microbial pathogens.\n          <\/jats:p>","DOI":"10.1128\/mbio.00174-23","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T13:00:26Z","timestamp":1686920426000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["A cathepsin C-like protease mediates the post-translation modification of\n            <i>Toxoplasma gondii<\/i>\n            secretory proteins for optimal invasion and egress"],"prefix":"10.1128","author":[{"given":"L. Brock","family":"Thornton","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Clemson University, Clemson, South Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Key","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Clemson University, Clemson, South Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Micchelli","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Clemson University, Clemson, South Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Stasic","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, USA"},{"name":"Department of Cellular Biology, University of Georgia, Athens, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Kwain","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Clemson University, Clemson, South Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Floyd","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Clemson University, Clemson, South Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2041-6295","authenticated-orcid":false,"given":"Silvia N.J.","family":"Moreno","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, USA"},{"name":"Department of Cellular Biology, University of Georgia, Athens, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian N.","family":"Dominy","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Clemson University, Clemson, South Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel C.","family":"Whitehead","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Clemson University, Clemson, South Carolina, USA"},{"name":"Eukaryotic Pathogens Innovation Center, Clemson University, Clemson, South Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1887-1181","authenticated-orcid":false,"given":"Zhicheng","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Clemson University, Clemson, South Carolina, USA"},{"name":"Eukaryotic Pathogens Innovation Center, Clemson University, Clemson, South Carolina, 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