PMID- 29040286 OWN - NLM STAT- MEDLINE DCOM- 20171030 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 10 DP - 2017 TI - Human babesiosis: Indication of a molecular mimicry between thrombospondin domains from a novel Babesia microti BmP53 protein and host platelets molecules. PG - e0185372 LID - 10.1371/journal.pone.0185372 [doi] LID - e0185372 AB - 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. FAU - Mousa, Ahmed Abdelmoniem AU - Mousa AA AD - Institut de Biologie Computationnelle (IBC), LIRMM, CNRS, Universite de Montpellier, Montpellier, France. AD - National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan. AD - Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Menoufia, Egypt. FAU - Roche, Daniel Barry AU - Roche DB AD - Institut de Biologie Computationnelle (IBC), LIRMM, CNRS, Universite de Montpellier, Montpellier, France. AD - Centre de Recherche en Biologie cellulaire de Montpellier, CNRS-UMR 5237, Montpellier, France. FAU - Terkawi, Mohamad Alaa AU - Terkawi MA AD - Institut de Biologie Computationnelle (IBC), LIRMM, CNRS, Universite de Montpellier, Montpellier, France. FAU - Kameyama, Kyohko AU - Kameyama K AD - National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan. FAU - Kamyingkird, Ketsarin AU - Kamyingkird K AD - National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan. AD - Department of Parasitology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, Thailand. FAU - Vudriko, Patrick AU - Vudriko P AD - National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan. FAU - Salama, Akram AU - Salama A AD - Department of Animal Medicine and Infectious Diseases, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Menoufia, Egypt. FAU - Cao, Shinuo AU - Cao S AD - National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan. FAU - Orabi, Sahar AU - Orabi S AD - Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Menoufia, Egypt. FAU - Khalifa, Hanem AU - Khalifa H AD - Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Menoufia, Egypt. FAU - Ahmed, Mohamed AU - Ahmed M AD - Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Menoufia, Egypt. FAU - Attia, Mabrouk AU - Attia M AD - Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Menoufia, Egypt. FAU - Elkirdasy, Ahmed AU - Elkirdasy A AD - Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Menoufia, Egypt. FAU - Nishikawa, Yoshifumi AU - Nishikawa Y AD - Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Menoufia, Egypt. FAU - Xuan, Xuenan AU - Xuan X AD - Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Menoufia, Egypt. FAU - Cornillot, Emmanuel AU - Cornillot E AUID- ORCID: 0000-0002-1202-1162 AD - Institut de Biologie Computationnelle (IBC), LIRMM, CNRS, Universite de Montpellier, Montpellier, France. AD - Institut de Recherche en Cancerologie de Montpellier (IRCM-INSERM U1194), Institut regional du Cancer Montpellier (ICM) and Universite de Montpellier, Montpellier, France. LA - eng PT - Journal Article DEP - 20171017 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antigens, Protozoan) RN - 0 (Protozoan Proteins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Thrombospondin 1) RN - EC 2.5.1.18 (Glutathione Transferase) SB - IM EIN - PLoS One. 2017 Dec 5;12 (12 ):e0189383. PMID: 29206874 MH - Amino Acid Sequence MH - Animals MH - Antigens, Protozoan/chemistry/genetics/*immunology MH - Babesia microti/genetics/*immunology/isolation & purification MH - Babesiosis/immunology/*parasitology MH - Binding Sites MH - Blood Platelets/*parasitology MH - Cloning, Molecular MH - Cricetulus MH - Erythrocytes/parasitology MH - Escherichia coli/genetics/metabolism MH - Gene Expression MH - Glutathione Transferase/genetics/metabolism MH - Humans MH - *Immune Evasion MH - Mice MH - Models, Molecular MH - Molecular Mimicry MH - Protein Binding MH - Protein Interaction Domains and Motifs MH - Protein Structure, Secondary MH - Protozoan Proteins/chemistry/genetics/*immunology MH - Recombinant Fusion Proteins/chemistry/genetics/immunology MH - Sequence Alignment MH - Sequence Homology, Amino Acid MH - Thrombospondin 1/chemistry/genetics/*immunology PMC - PMC5644982 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2017/10/19 06:00 MHDA- 2017/10/31 06:00 PMCR- 2017/10/17 CRDT- 2017/10/18 06:00 PHST- 2017/03/22 00:00 [received] PHST- 2017/09/12 00:00 [accepted] PHST- 2017/10/18 06:00 [entrez] PHST- 2017/10/19 06:00 [pubmed] PHST- 2017/10/31 06:00 [medline] PHST- 2017/10/17 00:00 [pmc-release] AID - PONE-D-17-10804 [pii] AID - 10.1371/journal.pone.0185372 [doi] PST - epublish SO - PLoS One. 2017 Oct 17;12(10):e0185372. doi: 10.1371/journal.pone.0185372. eCollection 2017.