51. Human babesiosis: Indication of a molecular mimicry between thrombospondin domains from a novel Babesia microti BmP53 protein and host platelets molecules.
- Author
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Mousa AA, Roche DB, Terkawi MA, Kameyama K, Kamyingkird K, Vudriko P, Salama A, Cao S, Orabi S, Khalifa H, Ahmed M, Attia M, Elkirdasy A, Nishikawa Y, Xuan X, and Cornillot E
- Subjects
- Amino Acid Sequence, Animals, Antigens, Protozoan chemistry, Antigens, Protozoan genetics, Babesia microti genetics, Babesia microti isolation & purification, Babesiosis immunology, Binding Sites, Cloning, Molecular, Cricetulus, Erythrocytes parasitology, Escherichia coli genetics, Escherichia coli metabolism, Gene Expression, Glutathione Transferase genetics, Glutathione Transferase metabolism, Humans, Mice, Models, Molecular, Molecular Mimicry, Protein Binding, Protein Interaction Domains and Motifs, Protein Structure, Secondary, Protozoan Proteins chemistry, Protozoan Proteins genetics, Recombinant Fusion Proteins chemistry, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins immunology, Sequence Alignment, Sequence Homology, Amino Acid, Thrombospondin 1 chemistry, Thrombospondin 1 genetics, Antigens, Protozoan immunology, Babesia microti immunology, Babesiosis parasitology, Blood Platelets parasitology, Immune Evasion, Protozoan Proteins immunology, Thrombospondin 1 immunology
- Abstract
Human babesiosis is caused by the apicomplexan parasite Babesia microti, which is of major public health concern in the United States and elsewhere, resulting in malaise and fatigue, followed by a fever and hemolytic anemia. In this paper we focus on the characterization of a novel B. microti thrombospondin domain (TSP1)-containing protein (BmP53) from the new annotation of the B. microti genome (locus 'BmR1_04g09041'). This novel protein (BmP53) had a single TSP1 and a transmembrane domain, with a short cytoplasmic tail containing a sub-terminal glutamine residue, but no signal peptide and Von Willebrand factor type A domains (VWA), which are found in classical thrombospondin-related adhesive proteins (TRAP). Co-localization assays of BmP53 and Babesia microti secreted antigen 1 (BmSA1) suggested that BmP53 might be a non-secretory membranous protein. Molecular mimicry between the TSP1 domain from BmP53 and host platelets molecules was indicated through different measures of sequence homology, phylogenetic analysis, 3D structure and shared epitopes. Indeed, hamster isolated platelets cross-reacted with mouse anti-BmP53-TSP1. Molecular mimicry are used to help parasites to escape immune defenses, resulting in immune evasion or autoimmunity. Furthermore, specific host reactivity was also detected against the TSP1-free part of BmP53 in infected hamster sera. In conclusion, the TSP1 domain mimicry might help in studying the mechanisms of parasite-induced thrombocytopenia, with the TSP1-free truncate of the protein representing a potential safe candidate for future vaccine studies.
- Published
- 2017
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