Toxoplasma gondii is a ubiquitous parasitic protozoan infecting humans and a wide variety of animals. Fast-replicating tachyzoites during acute infection and slowly growing bradyzoites during chronic infection are the two basic forms of T. gondii in intermediate hosts. Interconversion between the two contributes to the transmission and pathogenesis of this parasite. Secretory micronemal proteins are thought to mediate interactions with host cells and facilitate parasite invasion, therefore the majority of them are highly expressed in tachyzoites. Micronemal protein 13 (MIC13) is unique in that its expression is low in tachyzoites and is upregulated under bradyzoite-inducing conditions. Previous attempts to disrupt this gene were not successful, implying that it may play critical roles during parasite growth. However, in this study, MIC13 was successfully disrupted in type 1 strain RH and type 2 strain ME49 using CRISPR/Cas9-mediated gene disruption techniques. Consistent with its low expression in tachyzoites and increased expression under stress or bradyzoite-inducing conditions, MIC13-inactivated mutants displayed normal growth, host cell invasion, intracellular replication, and egress, as well as acute virulence at the tachyzoite stage. However, under stress conditions, such as high pH or oxygen limitation, MIC13-disrupted parasites showed significantly slower growth rates compared to the parental strains, suggesting that it is required for optimal parasite growth under bradyzoite-inducing or stress conditions. This is the first micronemal protein reported to have such expression pattern and function modes, which expands our understanding of the diverse functions of micronemal proteins.
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http://dx.doi.org/10.1007/s00436-018-06197-3 | DOI Listing |
PLoS Pathog
December 2024
University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017-CIIL-Center for Infection and Immunity of Lille, Lille, France.
Pathogenesis of Toxoplasma gondii in the intermediate host is based on the tachyzoite ability to divide rapidly to produce significant amount of daughter cells in a reduce time frame. The regulation of the cell-cycle specific expression program is therefore key to their proliferation. Transcriptional regulation has a crucial role in establishing this expression program and transcription factors regulates many aspects of tachyzoite cell cycle.
View Article and Find Full Text PDFmBio
December 2024
Division of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Lucknow, India.
parasites have a complex life cycle that transitions between mosquito and mammalian hosts, and undergo continuous cellular remodeling to adapt to various drastic environments. Following hepatocyte invasion, the parasite discards superfluous organelles for intracellular replication, and the remnant organelles undergo extensive branching and mature into hepatic merozoites. Autophagy is a ubiquitous eukaryotic process that permits the recycling of intracellular components.
View Article and Find Full Text PDFActa Trop
December 2024
Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea; Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Core Re-search Institute (CRI), Kyung Hee University, Seoul, 02447, Republic of Korea. Electronic address:
Protective efficacy assessment of toxoplasmosis vaccines, at least at the preclinical level, frequently involves lethal dose challenge infection. Nonetheless, their efficacies remain largely unexplored against low infection doses which better reflects how humans become infected in the real world. In this study, we compared the immunity elicited in mice that were heterologously immunized with recombinant baculovirus and virus-like particles expressing either the cyst wall protein (CST1) or microneme protein 8 (MIC8) of Toxoplasma gondii (T.
View Article and Find Full Text PDFPLoS Pathog
December 2024
Center for Infectious Diseases, Integrative Parasitology, Heidelberg University Medical School, Heidelberg, Germany.
Transmission of the malaria parasite Plasmodium to mosquitoes necessitates gamete egress from red blood cells to allow zygote formation and ookinete motility to enable penetration of the midgut epithelium. Both processes are dependent on the secretion of proteins from distinct sets of specialized vesicles. Inhibiting some of these proteins has shown potential for blocking parasite transmission to the mosquito.
View Article and Find Full Text PDFParasit Vectors
November 2024
Department of Microbiology and Parasitology; Anhui Province Key Laboratory of Zoonoses, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, People's Republic of China.
Background: TgMIC1, a soluble adhesion protein that typically facilitates parasite invasion, exhibited varying expression levels among distinct virulence strains of Chinese 1 Toxoplasma. This study aims to explore its role in immunological regulation and its association with diverse postinfection outcomes in Toxoplasma infection.
Methods: First, the mic1 knockout strain Wh3Δmic1 was generated and assessed for its virulence and proliferative capacity.
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