ArticlePLoS pathogens2014
A cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 28 citations in OpenAlex.
- Therapeutic Targeting and Role of Cysteine Proteases in the Life Cycle of Malaria Parasite.Current medicinal chemistry · 2025Review
- The Plasmodium circumsporozoite protein.Trends in parasitology · 2024Review
- Inhibitor of Cysteine Protease ofPathogens (Basel, Switzerland) · 2022Article
- Target-Based Virtual Screening of Natural Compounds Identifies a Potent Antimalarial With Selective Falcipain-2 Inhibitory Activity.Frontiers in pharmacology · 2022Article
- Transcriptional heterogeneity and tightly regulated changes in gene expression duringProceedings of the National Academy of Sciences of the United States of America · 2021Article
- A malaria parasite subtilisin propeptide-like protein is a potent inhibitor of the egress protease SUB1.The Biochemical journal · 2020Article
- Synthetic DNA Vaccines Adjuvanted with pIL-33 Drive Liver-Localized T Cells and Provide Protection fromVaccines · 2020Article
- Discovery of four new B-cell protective epitopes for malaria using Q beta virus-like particle as platform.NPJ vaccines · 2020Article
- malERA: An updated research agenda for basic science and enabling technologies in malaria elimination and eradication.PLoS medicine · 2017Review
- Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
Plasmodium parasites express a potent inhibitor of cysteine proteases (ICP) throughout their life cycle. To analyze the role of ICP in different life cycle stages, we generated a stage-specific knockout of the Plasmodium berghei ICP (PbICP). Excision of the pbicb gene occurred in infective sporozoites and resulted in impaired sporozoite invasion of hepatocytes, despite residual PbICP protein being detectable in sporozoites. The vast majority of these parasites invading a cultured hepatocyte cell line did not develop to mature liver stages, but the few that successfully developed hepatic merozoites were able to initiate a blood stage infection in mice. These blood stage parasites, now completely lacking PbICP, exhibited an attenuated phenotype but were able to infect mosquitoes and develop to the oocyst stage. However, PbICP-negative sporozoites liberated from oocysts exhibited defective motility and invaded mosquito salivary glands in low numbers. They were also unable to invade hepatocytes, confirming that control of cysteine protease activity is of critical importance for sporozoites. Importantly, transfection of PbICP-knockout parasites with a pbicp-gfp construct fully reversed these defects. Taken together, in P. berghei this inhibitor of the ICP family is essential for sporozoite motility but also appears to play a role during parasite development in hepatocytes and erythrocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.