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Generation of a genetically double-attenuated Plasmodium berghei parasite that fully arrests growth during late liver stage development.
PLoS 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 PDFA conserved Plasmodium nuclear protein is critical for late liver stage development.
Commun Biol
October 2024
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA.
Malaria, caused by Plasmodium parasites, imposes a significant health burden and live-attenuated parasites are being pursued as vaccines. Here, we report on the creation of a genetically attenuated parasite by the deletion of Plasmodium LINUP, encoding a liver stage nuclear protein. In the rodent parasite Plasmodium yoelii, LINUP expression was restricted to liver stage nuclei after the onset of liver stage schizogony.
View Article and Find Full Text PDF-encoded murine IL-6 impairs liver stage infection and elicits long-lasting sterilizing immunity.
Front Immunol
May 2023
Institut Pasteur, Université Paris Cité, CNRS ERL9195 and Inserm U1201, Unité de Biologie des Interactions Hôte Parasites, Paris, France.
Introduction: sporozoites (SPZ) inoculated by mosquitoes into the skin of the mammalian host migrate to the liver before infecting hepatocytes. Previous work demonstrated that early production of IL-6 in the liver is detrimental for the parasite growth, contributing to the acquisition of a long-lasting immune protection after immunization with live attenuated parasites.
Methods: Considering that IL-6 as a critical pro-inflammatory signal, we explored a novel approach whereby the parasite itself encodes for the murine IL-6 gene.
Dissecting The role of metacaspase-2 in malaria gametogenesis and sporogony.
Emerg Microbes Infect
December 2022
ICMR-National Institute of Malaria Research, New Delhi, India.
The family of apicomplexan specific proteins contains caspases-like proteins called "metacaspases". These enzymes are present in the malaria parasite but absent in human; therefore, these can be explored as potential drug targets. We deleted the MCA-2 gene from genome using a gene knockout strategy to decipher its precise function.
View Article and Find Full Text PDFPreclinical Trial of Traditional Plant Remedies for the Treatment of Complications of Gestational Malaria.
Medicines (Basel)
December 2021
Department of Biochemistry, Federal University of Technology, Owerri 460102, Nigeria.
Most pregnant women living in high malaria endemic regions of Nigeria use herbal remedies for the management of malaria-in-pregnancy, rather than the commonly prescribed drugs. Remedies common to this area involve a suspension of (AI) leaves and in some cases, a suspension containing a mixture of AI and (PS). This study examined the therapeutic efficacies of AI, PS, or a combination of AI and PS in a pregnant rat model for exoerythrocytic stages of parasite.
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