Novel insights from the Plasmodium falciparum sporozoite-specific proteome by probabilistic integration of 26 studies.
Journal
PLoS computational biology
ISSN: 1553-7358
Titre abrégé: PLoS Comput Biol
Pays: United States
ID NLM: 101238922
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
14
06
2020
accepted:
06
04
2021
revised:
12
05
2021
pubmed:
1
5
2021
medline:
28
8
2021
entrez:
30
4
2021
Statut:
epublish
Résumé
Plasmodium species, the causative agent of malaria, have a complex life cycle involving two hosts. The sporozoite life stage is characterized by an extended phase in the mosquito salivary glands followed by free movement and rapid invasion of hepatocytes in the human host. This transmission stage has been the subject of many transcriptomics and proteomics studies and is also targeted by the most advanced malaria vaccine. We applied Bayesian data integration to determine which proteins are not only present in sporozoites but are also specific to that stage. Transcriptomic and proteomic Plasmodium data sets from 26 studies were weighted for how representative they are for sporozoites, based on a carefully assembled gold standard for Plasmodium falciparum (Pf) proteins known to be present or absent during the sporozoite life stage. Of 5418 Pf genes for which expression data were available at the RNA level or at the protein level, 975 were identified as enriched in sporozoites and 90 specific to them. We show that Pf sporozoites are enriched for proteins involved in type II fatty acid synthesis in the apicoplast and GPI anchor synthesis, but otherwise appear metabolically relatively inactive in the salivary glands of mosquitos. Newly annotated hypothetical sporozoite-specific and sporozoite-enriched proteins highlight sporozoite-specific functions. They include PF3D7_0104100 that we identified to be homologous to the prominin family, which in human has been related to a quiescent state of cancer cells. We document high levels of genetic variability for sporozoite proteins, specifically for sporozoite-specific proteins that elicit antibodies in the human host. Nevertheless, we can identify nine relatively well-conserved sporozoite proteins that elicit antibodies and that together can serve as markers for previous exposure. Our understanding of sporozoite biology benefits from identifying key pathways that are enriched during this life stage. This work can guide studies of molecular mechanisms underlying sporozoite biology and potential well-conserved targets for marker and drug development.
Identifiants
pubmed: 33930021
doi: 10.1371/journal.pcbi.1008067
pii: PCOMPBIOL-D-20-01001
pmc: PMC8115857
doi:
Substances chimiques
Proteome
0
Protozoan Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008067Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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