{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T08:18:33Z","timestamp":1765354713883,"version":"3.37.3"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T00:00:00Z","timestamp":1596240000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T00:00:00Z","timestamp":1596240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"name":"National Key Basic Research Program","award":["2015CB150300"],"award-info":[{"award-number":["2015CB150300"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Parasitol Res"],"published-print":{"date-parts":[[2020,9]]},"DOI":"10.1007\/s00436-020-06818-w","type":"journal-article","created":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T14:04:23Z","timestamp":1596290663000},"page":"3013-3022","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A cysteine protease of Babesia microti and its interaction with tick cystatins"],"prefix":"10.1007","volume":"119","author":[{"given":"Nana","family":"Wei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanfang","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinmiao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongzhi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Houshuang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyan","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3383-1084","authenticated-orcid":false,"given":"Jinlin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,8,1]]},"reference":[{"key":"6818_CR1","doi-asserted-by":"publisher","unstructured":"Ascencio ME, Florin-Christensen M, Mamoun CB, Weir W, Shiels B, Schnittger L (2018) Cysteine proteinase C1A paralog profiles correspond with phylogenetic lineages of pathogenic piroplasmids. Vet Sci 5. https:\/\/doi.org\/10.3390\/vetsci5020041","DOI":"10.3390\/vetsci5020041"},{"key":"6818_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0076-6879(94)44003-4","volume":"244","author":"AJ Barrett","year":"1994","unstructured":"Barrett AJ (1994) Classification of peptidases. Methods Enzymol 244:1\u201315. https:\/\/doi.org\/10.1016\/0076-6879(94)44003-4","journal-title":"Methods Enzymol"},{"key":"6818_CR3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.ttbdis.2015.09.002","volume":"7","author":"T Carletti","year":"2016","unstructured":"Carletti T, Barreto C, Mesplet M, Mira A, Weir W, Shiels B, Oliva AG, Schnittger L, Florin-Christensen M (2016) Characterization of a papain-like cysteine protease essential for the survival of Babesia ovis merozoites. Ticks Tick Borne Dis 7:85\u201393. https:\/\/doi.org\/10.1016\/j.ttbdis.2015.09.002","journal-title":"Ticks Tick Borne Dis"},{"key":"6818_CR4","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1084\/jem.188.4.725","volume":"188","author":"JC Engel","year":"1998","unstructured":"Engel JC, Doyle PS, Hsieh I, McKerrow JH (1998a) Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection. J Exp Med 188:725\u2013734. https:\/\/doi.org\/10.1084\/jem.188.4.725","journal-title":"J Exp Med"},{"issue":"Pt 5","key":"6818_CR5","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1242\/jcs.111.5.597","volume":"111","author":"JC Engel","year":"1998","unstructured":"Engel JC, Doyle PS, Palmer J, Hsieh I, Bainton DF, McKerrow JH (1998b) Cysteine protease inhibitors alter Golgi complex ultrastructure and function in Trypanosoma cruzi. J Cell Sci 111(Pt 5):597\u2013606","journal-title":"J Cell Sci"},{"key":"6818_CR6","doi-asserted-by":"publisher","first-page":"674","DOI":"10.4103\/0972-5229.194017","volume":"20","author":"PK Guru","year":"2016","unstructured":"Guru PK, JC OH, Lehrke HD, Winters JL, Wilson JW (2016) Exchange transfusion for babesiosis when, how, and how long? Indian J Crit Care Med 20:674\u2013676. https:\/\/doi.org\/10.4103\/0972-5229.194017","journal-title":"Indian J Crit Care Med"},{"key":"6818_CR7","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/S0166-6851(01)00423-6","volume":"119","author":"PJ Holman","year":"2002","unstructured":"Holman PJ, Hsieh MM, Nix JL, Bendele KG, Wagner GG, Ball JM (2002) A cathepsin L-like cysteine protease is conserved among Babesia equi isolates. Mol Biochem Parasitol 119:295\u2013300. https:\/\/doi.org\/10.1016\/S0166-6851(01)00423-6","journal-title":"Mol Biochem Parasitol"},{"key":"6818_CR8","doi-asserted-by":"publisher","unstructured":"Huang Q, Cao J, Zhou Y, Huang J, Gong H, Zhang H, Zhu XQ, Zhou J (2017) Babesia microti Aldo-keto reductase-like protein involved in antioxidant and anti-parasite response. Front Microbiol 8(2006). https:\/\/doi.org\/10.3389\/fmicb.2017.02006","DOI":"10.3389\/fmicb.2017.02006"},{"key":"6818_CR9","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1021\/jm8013663","volume":"52","author":"ID Kerr","year":"2009","unstructured":"Kerr ID, Lee JH, Pandey KC, Harrison A, Sajid M, Rosenthal PJ, Brinen LS (2009) Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity. J Med Chem 52:852\u2013857. https:\/\/doi.org\/10.1021\/jm8013663","journal-title":"J Med Chem"},{"key":"6818_CR10","doi-asserted-by":"publisher","first-page":"16079","DOI":"10.1038\/nmicrobiol.2016.79","volume":"1","author":"JE Lemieux","year":"2016","unstructured":"Lemieux JE, Tran AD, Freimark L, Schaffner SF, Goethert H, Andersen KG, Bazner S, Li A, McGrath G, Sloan L, Vannier E, Milner D, Pritt B, Rosenberg E, Telford S 3rd, Bailey JA, Sabeti PC (2016) A global map of genetic diversity in Babesia microti reveals strong population structure and identifies variants associated with clinical relapse. Nat Microbiol 1:16079. https:\/\/doi.org\/10.1038\/nmicrobiol.2016.79","journal-title":"Nat Microbiol"},{"key":"6818_CR11","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1186\/s13071-016-1517-2","volume":"9","author":"LH Li","year":"2016","unstructured":"Li LH, Zhu D, Zhang CC, Zhang Y, Zhou XN (2016) Experimental transmission of Babesia microti by Rhipicephalus haemaphysaloides. Parasit Vectors 9:231. https:\/\/doi.org\/10.1186\/s13071-016-1517-2","journal-title":"Parasit Vectors"},{"key":"6818_CR12","doi-asserted-by":"publisher","first-page":"408","DOI":"10.2174\/156802612799362913","volume":"12","author":"M Marco","year":"2012","unstructured":"Marco M, Coteron JM (2012) Falcipain inhibition as a promising antimalarial target. Curr Top Med Chem 12:408\u2013444. https:\/\/doi.org\/10.2174\/156802612799362913","journal-title":"Curr Top Med Chem"},{"key":"6818_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.actatropica.2011.09.008","volume":"121","author":"TM Martins","year":"2012","unstructured":"Martins TM, do Rosario VE, Domingos A (2012) Expression and characterization of the Babesia bigemina cysteine protease BbiCPL1. Acta Trop 121:1\u20135. https:\/\/doi.org\/10.1016\/j.actatropica.2011.09.008","journal-title":"Acta Trop"},{"key":"6818_CR14","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/0169-4758(95)80039-5","volume":"11","author":"JH McKerrow","year":"1995","unstructured":"McKerrow JH, McGrath ME, Engel JC (1995) The cysteine protease of Trypanosoma cruzi as a model for antiparasite drug design. Parasitol Today 11:279\u2013282. https:\/\/doi.org\/10.1016\/0169-4758(95)80039-5","journal-title":"Parasitol Today"},{"key":"6818_CR15","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/1756-3305-3-113","volume":"3","author":"M Mesplet","year":"2010","unstructured":"Mesplet M, Echaide I, Dominguez M, Mosqueda JJ, Suarez CE, Schnittger L, Florin-Christensen M (2010) Bovipain-2, the falcipain-2 ortholog, is expressed in intraerythrocytic stages of the tick-transmitted hemoparasite Babesia bovis. Parasit Vectors 3:113. https:\/\/doi.org\/10.1186\/1756-3305-3-113","journal-title":"Parasit Vectors"},{"key":"6818_CR16","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.2174\/092986712799828355","volume":"19","author":"J Mosqueda","year":"2012","unstructured":"Mosqueda J, Olvera-Ramirez A, Aguilar-Tipacamu G, Canto GJ (2012) Current advances in detection and treatment of babesiosis. Curr Med Chem 19:1504\u20131518. https:\/\/doi.org\/10.2174\/092986712799828355","journal-title":"Curr Med Chem"},{"key":"6818_CR17","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/1471-2199-10-112","volume":"10","author":"AM Nijhof","year":"2009","unstructured":"Nijhof AM, Balk JA, Postigo M, Jongejan F (2009) Selection of reference genes for quantitative RT-PCR studies in Rhipicephalus (Boophilus) microplus and Rhipicephalus appendiculatus ticks and determination of the expression profile of Bm86. BMC Mol Biol 10:112. https:\/\/doi.org\/10.1186\/1471-2199-10-112","journal-title":"BMC Mol Biol"},{"key":"6818_CR18","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.exppara.2007.04.009","volume":"117","author":"K Okubo","year":"2007","unstructured":"Okubo K, Yokoyama N, Govind Y, Alhassan A, Igarashi I (2007) Babesia bovis: effects of cysteine protease inhibitors on in vitro growth. Exp Parasitol 117:214\u2013217. https:\/\/doi.org\/10.1016\/j.exppara.2007.04.009","journal-title":"Exp Parasitol"},{"key":"6818_CR19","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.abb.2016.05.017","volume":"603","author":"M Paireder","year":"2016","unstructured":"Paireder M, Mehofer U, Tholen S, Porodko A, Schahs P, Maresch D, Biniossek ML, van der Hoorn RA, Lenarcic B, Novinec M, Schilling O, Mach L (2016) The death enzyme CP14 is a unique papain-like cysteine proteinase with a pronounced S2 subsite selectivity. Arch Biochem Biophys 603:110\u2013117. https:\/\/doi.org\/10.1016\/j.abb.2016.05.017","journal-title":"Arch Biochem Biophys"},{"key":"6818_CR20","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1007\/s10822-013-9682-2","volume":"27","author":"B Perez","year":"2013","unstructured":"Perez B, Antunes S, Goncalves LM, Domingos A, Gomes JR, Gomes P, Teixeira C (2013) Toward the discovery of inhibitors of babesipain-1, a Babesia bigemina cysteine protease: in vitro evaluation, homology modeling and molecular docking studies. J Comput Aided Mol Des 27:823\u2013835. https:\/\/doi.org\/10.1007\/s10822-013-9682-2","journal-title":"J Comput Aided Mol Des"},{"key":"6818_CR21","doi-asserted-by":"publisher","unstructured":"Rawlings ND, Barrett AJ (1993) Evolutionary families of peptidases. Biochem J 290 ( Pt 1): 205-218. https:\/\/doi.org\/10.1042\/bj2900205","DOI":"10.1042\/bj2900205"},{"key":"6818_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0166-6851(01)00438-8","volume":"120","author":"M Sajid","year":"2002","unstructured":"Sajid M, McKerrow JH (2002) Cysteine proteases of parasitic organisms. Mol Biochem Parasitol 120:1\u201321. https:\/\/doi.org\/10.1016\/S0166-6851(01)00438-8","journal-title":"Mol Biochem Parasitol"},{"key":"6818_CR23","doi-asserted-by":"publisher","first-page":"35284","DOI":"10.1038\/srep35284","volume":"6","author":"JC Silva","year":"2016","unstructured":"Silva JC, Cornillot E, McCracken C, Usmani-Brown S, Dwivedi A, Ifeonu OO, Crabtree J, Gotia HT, Virji AZ, Reynes C, Colinge J, Kumar V, Lawres L, Pazzi JE, Pablo JV, Hung C, Brancato J, Kumari P, Orvis J, Tretina K, Chibucos M, Ott S, Sadzewicz L, Sengamalay N, Shetty AC, Su Q, Tallon L, Fraser CM, Frutos R, Molina DM, Krause PJ, Ben Mamoun C (2016) Genome-wide diversity and gene expression profiling of Babesia microti isolates identify polymorphic genes that mediate host-pathogen interactions. Sci Rep-Uk 6:35284. https:\/\/doi.org\/10.1038\/srep35284","journal-title":"Sci Rep-Uk"},{"key":"6818_CR24","doi-asserted-by":"publisher","first-page":"e0006512","DOI":"10.1371\/journal.pntd.0006512","volume":"12","author":"JL Siqueira-Neto","year":"2018","unstructured":"Siqueira-Neto JL, Debnath A, McCall LI, Bernatchez JA, Ndao M, Reed SL, Rosenthal PJ (2018) Cysteine proteases in protozoan parasites. PLoS Negl Trop Dis 12:e0006512. https:\/\/doi.org\/10.1371\/journal.pntd.0006512","journal-title":"PLoS Negl Trop Dis"},{"key":"6818_CR25","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.2174\/092986711795328328","volume":"18","author":"C Teixeira","year":"2011","unstructured":"Teixeira C, Gomes JR, Gomes P (2011) Falcipains, Plasmodium falciparum cysteine proteases as key drug targets against malaria. Curr Med Chem 18:1555\u20131572. https:\/\/doi.org\/10.2174\/092986711795328328","journal-title":"Curr Med Chem"},{"key":"6818_CR26","doi-asserted-by":"publisher","first-page":"e1000062","DOI":"10.1371\/journal.ppat.1000062","volume":"4","author":"N Tsuji","year":"2008","unstructured":"Tsuji N, Miyoshi T, Battsetseg B, Matsuo T, Xuan X, Fujisaki K (2008) A cysteine protease is critical for Babesia spp. transmission in Haemaphysalis ticks. PLoS Pathog 4:e1000062. https:\/\/doi.org\/10.1371\/journal.ppat.1000062","journal-title":"PLoS Pathog"},{"key":"6818_CR27","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/S1473-3099(14)71062-X","volume":"15","author":"E Vannier","year":"2015","unstructured":"Vannier E, Krause PJ (2015) Babesiosis in China, an emerging threat. Lancet Infect Dis 15:137\u2013139. https:\/\/doi.org\/10.1016\/S1473-3099(14)71062-X","journal-title":"Lancet Infect Dis"},{"key":"6818_CR28","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.idc.2008.03.010","volume":"22","author":"E Vannier","year":"2008","unstructured":"Vannier E, Gewurz BE, Krause PJ (2008) Human babesiosis. Infect Dis Clin N Am 22:469\u2013488, viii-ix. https:\/\/doi.org\/10.1016\/j.idc.2008.03.010","journal-title":"Infect Dis Clin N Am"},{"key":"6818_CR29","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.vetpar.2006.01.048","volume":"138","author":"HJ Vial","year":"2006","unstructured":"Vial HJ, Gorenflot A (2006) Chemotherapy against babesiosis. Vet Parasitol 138:147\u2013160. https:\/\/doi.org\/10.1016\/j.vetpar.2006.01.048","journal-title":"Vet Parasitol"},{"key":"6818_CR30","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s10493-015-9946-8","volume":"67","author":"Y Wang","year":"2015","unstructured":"Wang Y, Yu X, Cao J, Zhou Y, Gong H, Zhang H, Li X, Zhou J (2015a) Characterization of a secreted cystatin from the tick Rhipicephalus haemaphysaloides. Exp Appl Acarol 67:289\u2013298. https:\/\/doi.org\/10.1007\/s10493-015-9946-8","journal-title":"Exp Appl Acarol"},{"key":"6818_CR31","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1186\/s13071-015-0725-5","volume":"8","author":"Y Wang","year":"2015","unstructured":"Wang Y, Zhou Y, Gong H, Cao J, Zhang H, Li X, Zhou J (2015b) Functional characterization of a cystatin from the tick Rhipicephalus haemaphysaloides. Parasit Vectors 8:140. https:\/\/doi.org\/10.1186\/s13071-015-0725-5","journal-title":"Parasit Vectors"},{"key":"6818_CR32","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.ijppaw.2012.11.003","volume":"2","author":"MJ Yabsley","year":"2013","unstructured":"Yabsley MJ, Shock BC (2013) Natural history of zoonotic Babesia: role of wildlife reservoirs. Int J Parasitol Parasites Wildl 2:18\u201331. https:\/\/doi.org\/10.1016\/j.ijppaw.2012.11.003","journal-title":"Int J Parasitol Parasites Wildl"},{"key":"6818_CR33","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.parint.2009.05.003","volume":"58","author":"K Yamaji","year":"2009","unstructured":"Yamaji K, Tsuji N, Miyoshi T, Islam MK, Hatta T, Alim MA, Anisuzzaman TA, Fujisaki K (2009) Hemoglobinase activity of a cysteine protease from the ixodid tick Haemaphysalis longicornis. Parasitol Int 58:232\u2013237. https:\/\/doi.org\/10.1016\/j.parint.2009.05.003","journal-title":"Parasitol Int"},{"key":"6818_CR34","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.exppara.2016.08.005","volume":"170","author":"H Zhang","year":"2016","unstructured":"Zhang H, Wang Z, Gong H, Cao J, Zhou Y, Zhou J (2016) Identification and functional study of a novel 2-cys peroxiredoxin (BmTPx-1) of Babesia microti. Exp Parasitol 170:21\u201327. https:\/\/doi.org\/10.1016\/j.exppara.2016.08.005","journal-title":"Exp Parasitol"},{"key":"6818_CR35","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s00436-006-0243-7","volume":"100","author":"J Zhou","year":"2006","unstructured":"Zhou J, Gong H, Zhou Y, Xuan X, Fujisaki K (2006a) Identification of a glycine-rich protein from the tick Rhipicephalus haemaphysaloides and evaluation of its vaccine potential against tick feeding. Parasitol Res 100:77\u201384. https:\/\/doi.org\/10.1007\/s00436-006-0243-7","journal-title":"Parasitol Res"},{"key":"6818_CR36","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.ibmb.2006.03.003","volume":"36","author":"J Zhou","year":"2006","unstructured":"Zhou J, Ueda M, Umemiya R, Battsetseg B, Boldbaatar D, Xuan X, Fujisaki K (2006b) A secreted cystatin from the tick Haemaphysalis longicornis and its distinct expression patterns in relation to innate immunity. Insect Biochem Mol Biol 36:527\u2013535. https:\/\/doi.org\/10.1016\/j.ibmb.2006.03.003","journal-title":"Insect Biochem Mol Biol"}],"container-title":["Parasitology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00436-020-06818-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00436-020-06818-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00436-020-06818-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T23:57:06Z","timestamp":1627775826000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00436-020-06818-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,1]]},"references-count":36,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["6818"],"URL":"https:\/\/doi.org\/10.1007\/s00436-020-06818-w","relation":{},"ISSN":["0932-0113","1432-1955"],"issn-type":[{"type":"print","value":"0932-0113"},{"type":"electronic","value":"1432-1955"}],"subject":[],"published":{"date-parts":[[2020,8,1]]},"assertion":[{"value":"22 January 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 August 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Mice were maintained in a SPF facility under sterile atmosphere at the Animal Center of the Shanghai Veterinary Research Institute (IACUC approval number shvri-mo-2018010018). All animal experiments were authorized by the Animal Ethical Committee of Shanghai Veterinary Research Institute.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving animals"}}]}}