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...
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Publishing Group
2020-06-01
|
Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-020-66273-6 |
id |
doaj-d8b8d02928364355960511831323b8a1 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2020-06-01 |
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. |
url |
https://doi.org/10.1038/s41598-020-66273-6 |
work_keys_str_mv |
AT nitinverma antigendiscoverybioinformaticsandbiologicalcharacterizationofnovelimmunodominantbabesiamicrotiantigens AT ankitpuri antigendiscoverybioinformaticsandbiologicalcharacterizationofnovelimmunodominantbabesiamicrotiantigens AT edwardessuman antigendiscoverybioinformaticsandbiologicalcharacterizationofnovelimmunodominantbabesiamicrotiantigens AT richardskelton antigendiscoverybioinformaticsandbiologicalcharacterizationofnovelimmunodominantbabesiamicrotiantigens AT vivekanantharaman antigendiscoverybioinformaticsandbiologicalcharacterizationofnovelimmunodominantbabesiamicrotiantigens AT hongzheng antigendiscoverybioinformaticsandbiologicalcharacterizationofnovelimmunodominantbabesiamicrotiantigens AT sierawhite antigendiscoverybioinformaticsandbiologicalcharacterizationofnovelimmunodominantbabesiamicrotiantigens AT karthigayangunalan antigendiscoverybioinformaticsandbiologicalcharacterizationofnovelimmunodominantbabesiamicrotiantigens AT kazuyotakeda antigendiscoverybioinformaticsandbiologicalcharacterizationofnovelimmunodominantbabesiamicrotiantigens AT surabhibajpai antigendiscoverybioinformaticsandbiologicalcharacterizationofnovelimmunodominantbabesiamicrotiantigens AT timothyjlepore antigendiscoverybioinformaticsandbiologicalcharacterizationofnovelimmunodominantbabesiamicrotiantigens AT peterjkrause antigendiscoverybioinformaticsandbiologicalcharacterizationofnovelimmunodominantbabesiamicrotiantigens AT laravind antigendiscoverybioinformaticsandbiologicalcharacterizationofnovelimmunodominantbabesiamicrotiantigens AT sanjaikumar antigendiscoverybioinformaticsandbiologicalcharacterizationofnovelimmunodominantbabesiamicrotiantigens |
_version_ |
1721379517194305536 |
spelling |
doaj-d8b8d02928364355960511831323b8a12021-06-13T11:48:22ZengNature Publishing GroupScientific Reports2045-23222020-06-0110111510.1038/s41598-020-66273-6Antigen Discovery, Bioinformatics and Biological Characterization of Novel Immunodominant Babesia microti AntigensNitin Verma0Ankit Puri1Edward Essuman2Richard Skelton3Vivek Anantharaman4Hong Zheng5Siera White6Karthigayan Gunalan7Kazuyo Takeda8Surabhi Bajpai9Timothy J. Lepore10Peter J. Krause11L. Aravind12Sanjai Kumar13Laboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug AdministrationLaboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug AdministrationLaboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug AdministrationLaboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug AdministrationNational Center for Biotechnology Information, National Library of Medicine, National Institutes of HealthLaboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug AdministrationLaboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug AdministrationLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLab Of Method Development, Office of Vaccine Research and Review, Center for Biologics Evaluation and Research, Food and Drug AdministrationDepartment of Bioscience and Biotechnology, Banasthali VidyapithNantucket Cottage HospitalYale School of Public Health and Yale School of MedicineNational Center for Biotechnology Information, National Library of Medicine, National Institutes of HealthLaboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug AdministrationAbstract 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.https://doi.org/10.1038/s41598-020-66273-6 |