{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:25:05Z","timestamp":1789586705261,"version":"build-2803163510"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"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>\n                    <jats:italic>Cryptosporidium parvum<\/jats:italic>\n                    is an apicomplexan parasite and an important pathogen of mammals and humans, which can be infected by zoonotic transmission or directly by human-to-human contact. This parasite attacks the small intestine, and the main symptom is a watery diarrhea that can be particularly severe in newborns and deadly in immunodeficient subjects. Rhomboids are ubiquitous proteases embedded in cell membranes that act by cleaving other membrane proteins in or near their transmembrane domains. Apicomplexan rhomboids play an important role in approaching and invading the host cell. This study analyzed the phylogenetic origin, the structural motifs, and the subcellular localization of\n                    <jats:italic>C. parvum<\/jats:italic>\n                    rhomboids. Altogether,\n                    <jats:italic>C. parvum<\/jats:italic>\n                    possesses three rhomboids, namely, CpRom1, CpRom2, and CpRom3. The similarity search in\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    genus revealed that\n                    <jats:italic>C. parvum<\/jats:italic>\n                    and other \u201cintestinal\u201d species lack a PARL-like rhomboid whereas this type of mitochondrial rhomboid was present in \u201cgastric\u201d species like\n                    <jats:italic>Cryptosporidium muris<\/jats:italic>\n                    and\n                    <jats:italic>Cryptosporidium andersoni.<\/jats:italic>\n                    At the genome level, this was revealed by a precise excision of the PARL-like gene in intestinal species whereas the rest of chromosomal synteny was well conserved among the\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    species. The analysis of the structural domains revealed that\n                    <jats:italic>C. parvum<\/jats:italic>\n                    rhomboids can be classified as mixed secretases, and the comparison with orthologs from\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    and\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    showed that\n                    <jats:italic>C. parvum<\/jats:italic>\n                    rhomboids can be distinguished in two separate clusters based on similarities at the level of the catalytic sites. The three rhomboids were expressed simultaneously in the invasive stage of sporozoite, but each of them had a different spatial distribution. Indeed, CpRom1 had a dual localization: this rhomboid was internal at the apical complex, and it was also accumulated at the posterior pole of the sporozoite. Otherwise, CpRom2 was prevalently contained in the apical complex, and a point of accumulation was on the surface of the apical end. Differently from CpRom1 and CpRom2, CpRom3 is distributed along the entire surface of sporozoites. Finally, we listed 10 membrane proteins as candidate substrates for the\n                    <jats:italic>C. parvum<\/jats:italic>\n                    rhomboids based on the similarities with some proven substrates of apicomplexan rhomboids and the copresence in subcellular structures with the three rhomboids.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1733450","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T05:28:58Z","timestamp":1775539738000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploring the repertoire of rhomboid proteases in Cryptosporidium parvum parasite: phylogenesis, structural motifs, and cellular localization in sporozoite cells"],"prefix":"10.3389","volume":"16","author":[{"given":"Ilaria","family":"Vanni","sequence":"first","affiliation":[{"name":"Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Pizzi","sequence":"additional","affiliation":[{"name":"Core Facilities, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Bertuccini","sequence":"additional","affiliation":[{"name":"Core Facilities, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Ludovisi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Tosini","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1126\/science.1094786","article-title":"Complete genome sequence of the apicomplexan, Cryptosporidium parvum","volume":"304","author":"Abrahamsen","year":"2004","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e113","DOI":"10.1371\/journal.ppat.0020113","article-title":"Two Plasmodium rhomboid proteases preferentially cleave different adhesins implicated in all invasive stages of malaria","volume":"2","author":"Baker","year":"2006","journal-title":"PloS Pathog."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/6439375","article-title":"Cryptosporidiosis in a zoonotic gastrointestinal disorder perspective: present status, risk factors, pathophysiology, and treatment, particularly in immunocompromised patients","volume":"2024","author":"Balendran","year":"2024","journal-title":"J. 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