The Plasmodium Liver-Specific Protein 2 (LISP2) is an early marker of liver stage development
- Novartis Institute for Tropical Diseases, United States
- Université des Sciences, des Techniques et des Technologies de Bamako, Mali
- Biomedical Primate Research Centre, Netherlands
- Novartis Institutes for BioMedical Research, Switzerland
- Novartis Institute for Tropical Diseases, Singapore
- Center for Infectious Disease Research, United States
- Mahidol University, Thailand
- Ehime University, Japan
Abstract
Plasmodium vivax hypnozoites persist in the liver, cause malaria relapse and represent a major challenge to malaria elimination. Our previous transcriptomic study provided a novel molecular framework to enhance our understanding of the hypnozoite biology (Voorberg-van der Wel A, et al., 2017). In this dataset, we identified and characterized the Liver-Specific Protein 2 (LISP2) protein as an early molecular marker of liver stage development. Immunofluorescence analysis of hepatocytes infected with relapsing malaria parasites, in vitro (P. cynomolgi) and in vivo (P. vivax), reveals that LISP2 expression discriminates between dormant hypnozoites and early developing parasites. We further demonstrate that prophylactic drugs selectively kill all LISP2 positive parasites, while LISP2 negative hypnozoites are only sensitive to anti-relapse drug tafenoquine. Our results provide novel biological insights in the initiation of liver stage schizogony and an early marker suitable for the development of drug discovery assays predictive of anti-relapse activity.
Data availability
All data generated during the study are submitted as supplementary source files.
-
Malaria Liver Stages TranscriptomeNCBI Sequence Read Archive, SRP096160.
Article and author information
Author details
Annemarie Voorberg-van der Wel
Jetsumon Sattabongkot
Thierry Tidiane Diagana
Funding
Bill and Melinda Gates Foundation (OPP1141292)
- Guglielmo Roma
- Clemens H M Kocken
- Thierry Tidiane Diagana
Bill and Melinda Gates Foundation (OPP1137694)
- Sebastian A Mikolajczak
Funders have no role in the design of the study.
Ethics
Animal experimentation: Ethics statement included in the method section of the manuscript.
Copyright
© 2019, Gupta et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,884
- views
-
- 462
- downloads
-
- 51
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Further reading
-
- Microbiology and Infectious Disease
eLife has recently published a wide range of papers on malaria, covering a diversity of themes including parasite biology, epidemiology, immunology, drugs and vaccines.
-
- Microbiology and Infectious Disease
Saprolegnia parasitica is one of the most virulent oomycete species in freshwater aquatic environments, causing severe saprolegniasis and leading to significant economic losses in the aquaculture industry. Thus far, the prevention and control of saprolegniasis face a shortage of medications. Linalool, a natural antibiotic alternative found in various essential oils, exhibits promising antimicrobial activity against a wide range of pathogens. In this study, the specific role of linalool in protecting S. parasitica infection at both in vitro and in vivo levels was investigated. Linalool showed multifaceted anti-oomycetes potential by both of antimicrobial efficacy and immunomodulatory efficacy. For in vitro test, linalool exhibited strong anti-oomycetes activity and mode of action included: (1) Linalool disrupted the cell membrane of the mycelium, causing the intracellular components leak out; (2) Linalool prohibited ribosome function, thereby inhibiting protein synthesis and ultimately affecting mycelium growth. Surprisingly, meanwhile we found the potential immune protective mechanism of linalool in the in vivo test: (1) Linalool enhanced the complement and coagulation system which in turn activated host immune defense and lysate S. parasitica cells; (2) Linalool promoted wound healing, tissue repair, and phagocytosis to cope with S. parasitica infection; (3) Linalool positively modulated the immune response by increasing the abundance of beneficial Actinobacteriota; (4) Linalool stimulated the production of inflammatory cytokines and chemokines to lyse S. parasitica cells. In all, our findings showed that linalool possessed multifaceted anti-oomycetes potential which would be a promising natural antibiotic alternative to cope with S. parasitica infection in the aquaculture industry.
