Human babesiosis: Indication of a molecular mimicry between thrombospondin domains from a novel Babesia microti BmP53 protein and host platelets molecules

Ahmed Abdelmoniem Mousa,Ahmed Elkirdasy,Ketsarin Kamyingkird,Mohamed Ahmed,Patrick Vudriko,Akram Salama,Emmanuel Cornillot,Shinuo Cao,Kyohko Kameyama,Xuenan Xuan,Mohamad Alaa Terkawi,Sahar Orabi,Mabrouk Attia,Yoshifumi Nishikawa,Daniel Barry Roche,Hanem Khalifa

doi:10.1371/journal.pone.0185372

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.

Highlights

B. microti is a protozoan apicomplexan piroplasm, the causative agent of human babesiosis, endemic in the United States [1] and present in many other countries [2]
Bmicroti genome encodes for four TSP1 domains containing proteins according to InterPro database
B. microti strain R1 proteome was screened for thrombospondin type 1 domain-containing proteins (TSP1 domain)

Summary

Introduction

B. microti is a protozoan apicomplexan piroplasm, the causative agent of human babesiosis, endemic in the United States [1] and present in many other countries [2]. B. microti is transmitted through blood transfusion [3]. It causes asymptomatic to severe illness [1]. Onset of infection is often characterized by a flu-like syndrome associated with fever, chills and headache. The disease may evolve in an acute phase where the parasite start growing in patient blood leading to anemia and clinical complications resulting from hemolysis. Severe onset symptoms may include acute respiratory failure, organ failure and disseminated intravascular coagulation [4]. The disturbance of the coagulation system was described during veterinary infections with other Babesia species, which was involving kallikrein and non-identified factors [5, 6]

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Conclusion