Antigen Discovery, Bioinformatics and Biological Characterization of Novel Immunodominant Babesia microti Antigens

Abstract Babesia microti is an intraerythrocytic parasite and the primary causative agent of human babesiosis. It is transmitted by Ixodes ticks, transfusion of blood and blood products, organ donation, and perinatally. Despite its global public health impact, limited progress has been made to ident...

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Autores principales:	Nitin Verma, Ankit Puri, Edward Essuman, Richard Skelton, Vivek Anantharaman, Hong Zheng, Siera White, Karthigayan Gunalan, Kazuyo Takeda, Surabhi Bajpai, Timothy J. Lepore, Peter J. Krause, L. Aravind, Sanjai Kumar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d8b8d02928364355960511831323b8a1
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spelling	oai:doaj.org-article:d8b8d02928364355960511831323b8a12021-12-02T17:52:13ZAntigen Discovery, Bioinformatics and Biological Characterization of Novel Immunodominant Babesia microti Antigens10.1038/s41598-020-66273-62045-2322https://doaj.org/article/d8b8d02928364355960511831323b8a12020-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-66273-6https://doaj.org/toc/2045-2322Abstract Babesia microti is an intraerythrocytic parasite and the primary causative agent of human babesiosis. It is transmitted by Ixodes ticks, transfusion of blood and blood products, organ donation, and perinatally. Despite its global public health impact, limited progress has been made to identify and characterize immunodominant B. microti antigens for diagnostic and vaccine use. Using genome-wide immunoscreening, we identified 56 B. microti antigens, including some previously uncharacterized antigens. Thirty of the most immunodominant B. microti antigens were expressed as recombinant proteins in E. coli. Among these, the combined use of two novel antigens and one previously described antigen provided 96% sensitivity and 100% specificity in identifying B. microti antibody containing sera in an ELISA. Using extensive computational sequence and bioinformatics analyses and cellular localization studies, we have clarified the domain architectures, potential biological functions, and evolutionary relationships of the most immunodominant B. microti antigens. Notably, we found that the BMN-family antigens are not monophyletic as currently annotated, but rather can be categorized into two evolutionary unrelated groups of BMN proteins respectively defined by two structurally distinct classes of extracellular domains. Our studies have enhanced the repertoire of immunodominant B. microti antigens, and assigned potential biological function to these antigens, which can be evaluated to develop novel assays and candidate vaccines.Nitin VermaAnkit PuriEdward EssumanRichard SkeltonVivek AnantharamanHong ZhengSiera WhiteKarthigayan GunalanKazuyo TakedaSurabhi BajpaiTimothy J. LeporePeter J. KrauseL. AravindSanjai KumarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nitin Verma Ankit Puri Edward Essuman Richard Skelton Vivek Anantharaman Hong Zheng Siera White Karthigayan Gunalan Kazuyo Takeda Surabhi Bajpai Timothy J. Lepore Peter J. Krause L. Aravind Sanjai Kumar Antigen Discovery, Bioinformatics and Biological Characterization of Novel Immunodominant Babesia microti Antigens
description	Abstract Babesia microti is an intraerythrocytic parasite and the primary causative agent of human babesiosis. It is transmitted by Ixodes ticks, transfusion of blood and blood products, organ donation, and perinatally. Despite its global public health impact, limited progress has been made to identify and characterize immunodominant B. microti antigens for diagnostic and vaccine use. Using genome-wide immunoscreening, we identified 56 B. microti antigens, including some previously uncharacterized antigens. Thirty of the most immunodominant B. microti antigens were expressed as recombinant proteins in E. coli. Among these, the combined use of two novel antigens and one previously described antigen provided 96% sensitivity and 100% specificity in identifying B. microti antibody containing sera in an ELISA. Using extensive computational sequence and bioinformatics analyses and cellular localization studies, we have clarified the domain architectures, potential biological functions, and evolutionary relationships of the most immunodominant B. microti antigens. Notably, we found that the BMN-family antigens are not monophyletic as currently annotated, but rather can be categorized into two evolutionary unrelated groups of BMN proteins respectively defined by two structurally distinct classes of extracellular domains. Our studies have enhanced the repertoire of immunodominant B. microti antigens, and assigned potential biological function to these antigens, which can be evaluated to develop novel assays and candidate vaccines.
format	article
author	Nitin Verma Ankit Puri Edward Essuman Richard Skelton Vivek Anantharaman Hong Zheng Siera White Karthigayan Gunalan Kazuyo Takeda Surabhi Bajpai Timothy J. Lepore Peter J. Krause L. Aravind Sanjai Kumar
author_facet	Nitin Verma Ankit Puri Edward Essuman Richard Skelton Vivek Anantharaman Hong Zheng Siera White Karthigayan Gunalan Kazuyo Takeda Surabhi Bajpai Timothy J. Lepore Peter J. Krause L. Aravind Sanjai Kumar
author_sort	Nitin Verma
title	Antigen Discovery, Bioinformatics and Biological Characterization of Novel Immunodominant Babesia microti Antigens
title_short	Antigen Discovery, Bioinformatics and Biological Characterization of Novel Immunodominant Babesia microti Antigens
title_full	Antigen Discovery, Bioinformatics and Biological Characterization of Novel Immunodominant Babesia microti Antigens
title_fullStr	Antigen Discovery, Bioinformatics and Biological Characterization of Novel Immunodominant Babesia microti Antigens
title_full_unstemmed	Antigen Discovery, Bioinformatics and Biological Characterization of Novel Immunodominant Babesia microti Antigens
title_sort	antigen discovery, bioinformatics and biological characterization of novel immunodominant babesia microti antigens
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/d8b8d02928364355960511831323b8a1
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Antigen Discovery, Bioinformatics and Biological Characterization of Novel Immunodominant Babesia microti Antigens

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