The apicoplast of Plasmodium falciparum is the only source of essential isoprenoid precursors and Coenzyme A (CoA) in the parasite. Isoprenoid precursor synthesis relies on the iron-sulfur cluster (FeS) cofactors produced within the apicoplast, rendering FeS synthesis an essential function of this organelle. Recent reports provide important insights into the roles of FeS cofactors and the use of isoprenoid precursors and CoA both inside and outside the apicoplast. Here, we review the recent insights into the roles of these metabolites in blood-stage malaria parasites and discuss new questions that have been raised in light of these discoveries.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9852000 | PMC |
http://dx.doi.org/10.1016/j.mib.2022.102255 | DOI Listing |
Int J Parasitol Drugs Drug Resist
December 2024
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD, 21210, USA. Electronic address:
Fosmidomycin and clindamycin target the Plasmodium apicoplast. Combination clinical trials have produced mixed results with the primary problem being the recrudescent infection frequency by day 28. Given that antibiotic efficacy against bacterial infections often depends on the constant drug presence over several days, we hypothesized that the antimalarial blood or liver stage efficacy of fosmidomycin and clindamycin could be improved by implementing a more frequent dosing schedule.
View Article and Find Full Text PDFPLoS One
December 2024
Institute of Cell Biology, University of Bern, Bern, Switzerland.
Malaria caused by Plasmodium parasites remains a large health burden. One approach to combat this disease involves vaccinating individuals with whole sporozoites that have been genetically modified to arrest their development at a specific stage in the liver by targeted gene deletion, resulting in a genetically attenuated parasite (GAP). Through a comprehensive phenotyping screen, we identified the hscb gene, encoding a putative iron-sulfur protein assembly chaperone, as crucial for liver stage development, making it a suitable candidate gene for GAP generation.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
Malaria Biochemistry Laboratory, The Francis Crick Institute, 1 Midland Road, NW1 1AT London, UK.
The malaria parasite needs nearly half of its genes to propagate normally within red blood cells. Inducible ways to interfere with gene expression like the DiCre-lox system are necessary to study the function of these essential genes. However, existing DiCre-lox strategies are not well-suited to be deployed at scale to study several genes simultaneously.
View Article and Find Full Text PDFCharacterization of serological responses to Plasmodium falciparum (Pf) is of interest to understand disease burden and transmission dynamics; however, their interpretation is challenging. Dried blood spots from 30,815 participants aged 6 months to 15 years from the 2018 Nigeria HIV/AIDS Indicator and Impact Survey were analyzed by multiplex bead-based assay to measure immunoglobulin G (IgG) to Pf-stage-specific MSP-1, AMA-1, GLURPR0, LSA-1, and CSP. These IgG levels were analyzed by principal component analysis (PCA).
View Article and Find Full Text PDFFront Immunol
December 2024
Division of Infectious Diseases, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Introduction: Malaria remains a significant burden, and a fully protective vaccine against is critical for reducing morbidity and mortality. Antibody responses against the blood-stage antigen Merozoite Surface Protein 2 (MSP2) are associated with protection from malaria, but its extensive polymorphism is a barrier to its development as a vaccine candidate. New tools, such as long-read sequencing and accurate protein structure modelling allow us to study the genetic diversity and immune responses towards antigens from clinical isolates with unprecedented detail.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!