Abstract
Human babesiosis is a vector-borne zoonotic infection caused mostly by the Apicomplexan parasite Babesia microti, distributed worldwide. The infection can result in severe symptoms such as hemolytic anemia, especially in immunodeficient patients. Also, asymptomatic patients continue transmission as unscreened blood donors, and represent a risk for Public Health. Early host-parasite interactions are mediated by BmSA1, the major surface antigen of Babesia microti, crucial for invasion and immune escape. Hence, a structural and functional characterization of the BmSA1 protein constitutes a first strategic milestone toward the development of innovative tools to control infection. Knowledge of the 3D structure of such an important antigen is crucial for the development of vaccines or new diagnostic tests. Here, we report the 1H, 15N and 13C NMR resonance assignment of ∆∆BmSA1, a truncated recombinant version of BmSA1 without the N-terminal signal peptide and the hydrophobic C-terminal GPI-anchor. Secondary structure prediction using CSI.3 and TALOS-N demonstrates a high content of alpha-helical structure. This preliminary study provides foundations for further structural characterization of BMSA1.
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References
Delbecq S (2022) Major surface antigens in zoonotic babesia. Pathogens. https://doi.org/10.3390/pathogens11010099
Hafsa NE, Arndt D, Wishart DS (2015) CSI 3.0: a web server for identifying secondary and super-secondary structure in proteins using NMR chemical shifts. Nucleic Acids Res 43:W370–W377. https://doi.org/10.1093/nar/gkv494
Lee W, Tonelli M, Markley JL (2015) NMRFAM-SPARKY: enhanced software for biomolecular NMR spectroscopy. Bioinformatics 31:1325–1327. https://doi.org/10.1093/bioinformatics/btu830
Leiby DA (2011) Transfusion–transmitted Babesia spp.: bull’s-eye on Babesia microti. Clin Microbiol Rev 24:14–28. https://doi.org/10.1128/CMR.00022-10
Li M, Ao Y, Guo J, Nie Z, Liu Q, Yu L, Luo X, Zhan X, Zhao Y, Wang S, An X, He L, Zhao J (2020) Surface Antigen 1 is a crucial secreted protein that mediates Babesia microti invasion into host cells. Front Microbiol 10:1–10. https://doi.org/10.3389/fmicb.2019.03046
Man S, Fu Y, Guan Y, Feng M, Qiao K, Li X, Gao H, Cheng X (2017) Evaluation of a major surface antigen of Babesia microti merozoites as a vaccine candidate against Babesia infection. Front Microbiol 8:1–12. https://doi.org/10.3389/fmicb.2017.02545
Nathaly Wieser S, Schnittger L, Florin-Christensen M, Delbecq S, Schetters T (2019) Vaccination against babesiosis using recombinant GPI-anchored proteins. Int J Parasitol 49:175–181. https://doi.org/10.1016/j.ijpara.2018.12.002
Piotto M, Saudek V, Sklenár V (1992) Gradient-tailored excitation for single-quantum NMR spectroscopy of aqueous solutions. J Biomol NMR 2:661–665. https://doi.org/10.1007/BF02192855
Puri A, Bajpai S, Meredith S, Aravind L, Krause PJ, Kumar S (2021) Babesia microti: pathogen genomics, genetic variability, immunodominant antigens, and pathogenesis. Front Microbiol. https://doi.org/10.3389/fmicb.2021.697669
Sattler M (1999) Heteronuclear multidimensional NMR experiments for the structure determination of proteins in solution employing pulsed field gradients. Prog Nucl Magn Reson Spectrosc 34:93–158. https://doi.org/10.1016/S0079-6565(98)00025-9
Shen Y, Bax A (2013) Protein backbone and sidechain torsion angles predicted from NMR chemical shifts using artificial neural networks. J Biomol NMR 56:227–241. https://doi.org/10.1007/s10858-013-9741-y
Thekkiniath J, Mootien S, Lawres L, Perrin BA, Gewirtz M, Krause PJ, Williams S, Doggett JS, Ledizet M, Mamoun CB (2018) BmGPAC, an antigen capture assay for detection of active babesia microti infection. J Clin Microbiol 56:1–12. https://doi.org/10.1128/JCM.00067-18
Wishart DS, Sykes BD (1994) Chemical shifts as a tool for structure determination. Methods Enzymol 239:363–392. https://doi.org/10.1016/S0076-6879(94)39014-2
Wishart DS, Sykes BD, Richards FM (1992) The chemical shift index: a fast and simple method for the assignment of protein secondary structure through NMR spectroscopy. Biochemistry 31:1647–1651. https://doi.org/10.1021/bi00121a010
Zhang H, Neal S, Wishart DS (2003) RefDB: a database of uniformly referenced protein chemical shifts. J Biomol NMR 25:173–195. https://doi.org/10.1023/A:1022836027055
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This project was supported by French Infrastructure for Integrated Structural Biology (FRISBI) Grant No. ANR-10-INSB-05.
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AM, JP and SD sub-cloned, expressed and purified the recombinant protein. AM recorded and analyzed the NMR spectra with PB and CR. She also prepared the figures and contributed to the writing. CR and AM wrote the manuscript. SD found the funding and coordinate the project with CR. All authors reviewed the manuscript.
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Mouhand, A., Pissarra, J., Delbecq, S. et al. 1H, 13C and 15N backbone and side-chain resonance assignments of ∆∆BmSA1, the surface antigen of Babesia microti. Biomol NMR Assign 17, 217–221 (2023). https://doi.org/10.1007/s12104-023-10144-4
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DOI: https://doi.org/10.1007/s12104-023-10144-4