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

Amino Acid Sequence Animals Antibodies, Protozoan / immunology Antigens, Protozoan / genetics Babesia microti / genetics Babesiosis / immunology Case-Control Studies Computational Biology / methods Genetic Variation Genome Humans Immunodominant Epitopes / genetics Mice Mice, Inbred BALB C Mice, Inbred DBA Peptide Library Recombinant Proteins / genetics Sequence Homology

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
12 06 2020
Historique:
received: 17 05 2018
accepted: 11 05 2020
entrez: 14 6 2020
pubmed: 14 6 2020
medline: 15 12 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41598-020-66273-6 PMID: 32533024 PMC: PMC7293334
pubmed: 32533024
doi: 10.1038/s41598-020-66273-6
pii: 10.1038/s41598-020-66273-6
pmc: PMC7293334
doi:

Substances chimiques

Antibodies, Protozoan 0
Antigens, Protozoan 0
Immunodominant Epitopes 0
Peptide Library 0
Recombinant Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

9598

Subventions

Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : FDA HHS
ID : NA
Pays : United States

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Auteurs

Nitin Verma (N)

Laboratory 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 Administration, Silver Spring, MD, 20993, USA.

Ankit Puri (A)

Laboratory 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 Administration, Silver Spring, MD, 20993, USA.

Edward Essuman (E)

Laboratory 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 Administration, Silver Spring, MD, 20993, USA.

Richard Skelton (R)

Laboratory 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 Administration, Silver Spring, MD, 20993, USA.

Vivek Anantharaman (V)

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.

Hong Zheng (H)

Laboratory 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 Administration, Silver Spring, MD, 20993, USA.

Siera White (S)

Laboratory 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 Administration, Silver Spring, MD, 20993, USA.

Karthigayan Gunalan (K)

Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA.

Kazuyo Takeda (K)

Lab Of Method Development, Office of Vaccine Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA.

Surabhi Bajpai (S)

Department of Bioscience and Biotechnology, Banasthali Vidyapith, Banasthali, 304022, India.

Timothy J Lepore (TJ)

Nantucket Cottage Hospital, Nantucket, MA, 02554, USA.

Peter J Krause (PJ)

Yale School of Public Health and Yale School of Medicine, New Haven, CT, 06520, USA.

L Aravind (L)

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.

Sanjai Kumar (S)

Laboratory 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 Administration, Silver Spring, MD, 20993, USA. Sanjai.Kumar@fda.hhs.gov.

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