{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T15:09:42Z","timestamp":1761491382933,"version":"build-2065373602"},"reference-count":58,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T00:00:00Z","timestamp":1647043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Babesia bovis, a tick-transmitted apicomplexan protozoon, infects cattle in tropical and subtropical regions around the world. In the apicomplexans Toxoplasma gondii and Plasmodium falciparum, rhomboid serine protease 4 (ROM4) fulfills an essential role in host cell invasion. We thus investigated B. bovis ROM4 coding genes; their genomic organization; their expression in in vitro cultured asexual (AS) and sexual stages (SS); and strain polymorphisms. B. bovis contains five rom4 paralogous genes in chromosome 2, which we have named rom4.1, 4.2, 4.3, 4.4 and 4.5. There are moderate degrees of sequence identity between them, except for rom4.3 and 4.4, which are almost identical. RT-qPCR analysis showed that rom4.1 and rom4.3\/4.4, respectively, display 18-fold and 218-fold significantly higher (p &lt; 0.01) levels of transcription in SS than in AS, suggesting a role in gametogenesis-related processes. In contrast, transcription of rom4.4 and 4.5 differed non-significantly between the stages. ROM4 polymorphisms among geographic isolates were essentially restricted to the number of tandem repeats of a 29-amino acid sequence in ROM4.5. This sequence repeat is highly conserved and predicted as antigenic. B. bovis ROMs likely participate in relevant host\u2013pathogen interactions and are possibly useful targets for the development of new control strategies against this pathogen.<\/jats:p>","DOI":"10.3390\/pathogens11030344","type":"journal-article","created":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T21:44:17Z","timestamp":1647207857000},"page":"344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Unraveling the Complexity of the Rhomboid Serine Protease 4 Family of Babesia bovis Using Bioinformatics and Experimental Studies"],"prefix":"10.3390","volume":"11","author":[{"given":"Romina","family":"Gallenti","sequence":"first","affiliation":[{"name":"Instituto de Patobiolog\u00eda Veterinaria (IPVET), Centro de Investigaciones en Ciencias Veterinarias y Agron\u00f3micas, Instituto Nacional de Tecnolog\u00eda Agropecuaria\u2014Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (INTA-CONICET), Hurlingham 1686, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires C1033AAJ, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1912-2377","authenticated-orcid":false,"given":"Hala E.","family":"Hussein","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA"},{"name":"Department of Entomology, Faculty of Science, Cairo University, Giza 12613, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0260-7813","authenticated-orcid":false,"given":"Heba F.","family":"Alzan","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA"},{"name":"Tick and Tick-Borne Disease Research Unit, National Research Center, Giza 12622, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6112-2931","authenticated-orcid":false,"given":"Carlos E.","family":"Suarez","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA"},{"name":"US Department of Agriculture, Animal Disease Research Unit, (USDA-ARS), Pullman, WA 99163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massaro","family":"Ueti","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA"},{"name":"US Department of Agriculture, Animal Disease Research Unit, (USDA-ARS), Pullman, WA 99163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebasti\u00e1n","family":"Asurmendi","sequence":"additional","affiliation":[{"name":"Instituto de Agrobiotecnolog\u00eda y Biolog\u00eda Molecular (IABiMo), Instituto Nacional de Tecnolog\u00eda Agropecuaria\u2014Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (INTA-CONICET), Hurlingham 1686, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Benitez","sequence":"additional","affiliation":[{"name":"Estaci\u00f3n Experimental Agropecuaria (EEA)-Mercedes, Instituto Nacional de Tecnolog\u00eda Agropecuaria (INTA), Mercedes 3470, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flabio R.","family":"Araujo","sequence":"additional","affiliation":[{"name":"EMBRAPA Beef Cattle, Campo Grande 79106-550, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Rolls","sequence":"additional","affiliation":[{"name":"Department of Agriculture & Fisheries, Tick Fever Centre, Wacol, QLD 4076, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1139-7333","authenticated-orcid":false,"given":"Kgomotso","family":"Sibeko-Matjila","sequence":"additional","affiliation":[{"name":"Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Onderstepoort 0110, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3484-5370","authenticated-orcid":false,"given":"Leonhard","family":"Schnittger","sequence":"additional","affiliation":[{"name":"Instituto de Patobiolog\u00eda Veterinaria (IPVET), Centro de Investigaciones en Ciencias Veterinarias y Agron\u00f3micas, Instituto Nacional de Tecnolog\u00eda Agropecuaria\u2014Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (INTA-CONICET), Hurlingham 1686, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires C1033AAJ, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-3970","authenticated-orcid":false,"given":"M\u00f3nica","family":"Florin-Christensen","sequence":"additional","affiliation":[{"name":"Instituto de Patobiolog\u00eda Veterinaria (IPVET), Centro de Investigaciones en Ciencias Veterinarias y Agron\u00f3micas, Instituto Nacional de Tecnolog\u00eda Agropecuaria\u2014Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (INTA-CONICET), Hurlingham 1686, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires C1033AAJ, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1017\/S0031182014000961","article-title":"Vaccines against bovine babesiosis: Where we are now and possible roads 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