Mass Spectrometry Identification of Biomarkers in Extracellular Vesicles from Plasmodium vivax Liver Hypnozoite Infections
Issued Date
2022-10-01
Resource Type
ISSN
15359476
eISSN
15359484
Scopus ID
2-s2.0-85140041842
Pubmed ID
36030044
Journal Title
Molecular and Cellular Proteomics
Volume
21
Issue
10
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecular and Cellular Proteomics Vol.21 No.10 (2022)
Suggested Citation
Gualdrón-López M., Díaz-Varela M., Zanghi G., Aparici-Herraiz I., Steel R.W.J., Schäfer C., Cuscó P., Chuenchob V., Kangwangransan N., Billman Z.P., Olsen T.M., González J.R., Roobsoong W., Sattabongkot J., Murphy S.C., Mikolajczak S.A., Borràs E., Sabidó E., Fernandez-Becerra C., Flannery E.L., Kappe S.H.I., del Portillo H.A. Mass Spectrometry Identification of Biomarkers in Extracellular Vesicles from Plasmodium vivax Liver Hypnozoite Infections. Molecular and Cellular Proteomics Vol.21 No.10 (2022). doi:10.1016/j.mcpro.2022.100406 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/83593
Title
Mass Spectrometry Identification of Biomarkers in Extracellular Vesicles from Plasmodium vivax Liver Hypnozoite Infections
Author(s)
Gualdrón-López M.
Díaz-Varela M.
Zanghi G.
Aparici-Herraiz I.
Steel R.W.J.
Schäfer C.
Cuscó P.
Chuenchob V.
Kangwangransan N.
Billman Z.P.
Olsen T.M.
González J.R.
Roobsoong W.
Sattabongkot J.
Murphy S.C.
Mikolajczak S.A.
Borràs E.
Sabidó E.
Fernandez-Becerra C.
Flannery E.L.
Kappe S.H.I.
del Portillo H.A.
Díaz-Varela M.
Zanghi G.
Aparici-Herraiz I.
Steel R.W.J.
Schäfer C.
Cuscó P.
Chuenchob V.
Kangwangransan N.
Billman Z.P.
Olsen T.M.
González J.R.
Roobsoong W.
Sattabongkot J.
Murphy S.C.
Mikolajczak S.A.
Borràs E.
Sabidó E.
Fernandez-Becerra C.
Flannery E.L.
Kappe S.H.I.
del Portillo H.A.
Author's Affiliation
Faculty of Tropical Medicine, Mahidol University
Instituto de Salud Global de Barcelona
Universitat Pompeu Fabra Barcelona
Institució Catalana de Recerca i Estudis Avançats
University of Washington
Mahidol University
Seattle Biomedical Research Institute
Centro de Regulacion Genomica, Barcelona
IGTP
Instituto de Salud Global de Barcelona
Universitat Pompeu Fabra Barcelona
Institució Catalana de Recerca i Estudis Avançats
University of Washington
Mahidol University
Seattle Biomedical Research Institute
Centro de Regulacion Genomica, Barcelona
IGTP
Other Contributor(s)
Abstract
Latent liver stages termed hypnozoites cause relapsing Plasmodium vivax malaria infection and represent a major obstacle in the goal of malaria elimination. Hypnozoites are clinically undetectable, and presently, there are no biomarkers of this persistent parasite reservoir in the human liver. Here, we have identified parasite and human proteins associated with extracellular vesicles (EVs) secreted from in vivo infections exclusively containing hypnozoites. We used P. vivax-infected human liver-chimeric (huHEP) FRG KO mice treated with the schizonticidal experimental drug MMV048 as hypnozoite infection model. Immunofluorescence-based quantification of P. vivax liver forms showed that MMV048 removed schizonts from chimeric mice livers. Proteomic analysis of EVs derived from FRG huHEP mice showed that human EV cargo from infected FRG huHEP mice contain inflammation markers associated with active schizont replication and identified 66 P. vivax proteins. To identify hypnozoite-specific proteins associated with EVs, we mined the proteome data from MMV048-treated mice and performed an analysis involving intragroup and intergroup comparisons across all experimental conditions followed by a peptide compatibility analysis with predicted spectra to warrant robust identification. Only one protein fulfilled this stringent top-down selection, a putative filamin domain-containing protein. This study sets the stage to unveil biological features of human liver infections and identify biomarkers of hypnozoite infection associated with EVs.