Identification of three novel Toxoplasma gondii rhoptry proteins.
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ABSTRACT:
SUBMITTER: Camejo A
PROVIDER: S-EPMC3946946 | biostudies-literature | 2014 Feb
REPOSITORIES: biostudies-literature
Publications
Identification of three novel Toxoplasma gondii rhoptry proteins.
Camejo Ana A Gold Daniel A DA Lu Diana D McFetridge Kiva K Julien Lindsay L Yang Ninghan N Jensen Kirk D C KD Saeij Jeroen P J JP
International journal for parasitology 20130924 2
The rhoptries are key secretory organelles from apicomplexan parasites that contain proteins involved in invasion and modulation of the host cell. Some rhoptry proteins are restricted to the posterior bulb (ROPs) and others to the anterior neck (RONs). As many rhoptry proteins have been shown to be key players in Toxoplasma invasion and virulence, it is important to identify, understand and characterise the biological function of the components of the rhoptries. In this report, we identified put ...[more]
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Project description:Toxoplasmosis is a cosmopolitan zoonotic infection, caused by a unicellular protozoan parasite known as Toxoplasma gondii that belongs to the phylum Apicomplexa. It is estimated that over one-third of the world's population has been exposed and are latently infected with the parasite. In humans, toxoplasmosis is predominantly asymptomatic in immunocompetent persons, while among immunocompromised individuals may be cause severe and progressive complications with poor prognosis. Moreover, seronegative pregnant mothers are other risk groups for acquiring the infection. The life cycle of T. gondii is very complex, indicating the presence of a plurality of antigenic epitopes. Despite of great advances, recognize and construct novel vaccines for prevent and control of toxoplasmosis in both humans and animals is still remains a great challenge for researchers to select potential protein sequences as the ideal antigens. Notably, in several past years, constant efforts of researchers have made considerable advances to elucidate the different aspects of the cell and molecular biology of T. gondii mainly on microneme antigens, dense granule antigens, surface antigens, and rhoptry proteins (ROP). These attempts thereby provided great impetus to the present focus on vaccine development, according to the defined subcellular components of the parasite. Although, currently there is no commercial vaccine for use in humans. Among the main identified T. gondii antigens, ROPs appear as a putative vaccine candidate that are vital for invasion procedure as well as survival within host cells. Overall, it is estimated that they occupy about 1%-30% of the total parasite cell volume. In this review, we have summarized the recent progress of ROP-based vaccine development through various strategies from DNA vaccines, epitope or multi epitope-based vaccines, recombinant protein vaccines to vaccines based on live-attenuated vectors and prime-boost strategies in different mouse models.
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2022-10-20 | PXD031164 | Pride
Project description:Apicomplexan parasites, together with ciliates and dinoflagellates, belong to the Alveolata superphylum. Apicomplexa possess secretory organelles called rhoptries that undergo regulated exocytosis during invasion. Upon injection into the host cell, rhoptry proteins support invasion, vacuole formation, and subversion of host immune function. Rhoptry exocytosis involves a “rosette” of 8 particles embedded in the plasma membrane; such peculiar structure is also conserved in Ciliata and its formation requires Alveolata-restricted “Nd” proteins. These findings point to the existence of an Alveolata-conserved mechanism for the discharge of secretory organelles, and provide proof of concept that we can decipher rhoptry exocytosis machinery using a PAN-Alveolata approach. Thus, to uncover new rhoptry secretion factors, we used the transcriptional profiles of Nd genes of the ciliate Tetrahymena thermophila to select genes that are co-regulated, and also conserved in Apicomplexa. In this way we identified two uncharacterized Tetrahymena proteins that contribute to the exocytosis of secretory organelles. They have similar architecture and show homology with Plasmodium Cysteine Repeat Modular Proteins (CRMPs), a family of proteins essential for Plasmodium transmission from the mosquito to the host. We functionally characterized the two Toxoplasma CRMPs, including their dynamic location during invasion. They are not required for rosette formation, but they are essential for rhoptry secretion, suggesting a function distinct from that of previously characterized exocytic “Nd” factors. To characterize interacting proteins we performed pull-down experiments and analyzed the eluates by liquid chromatography-tandem mass spectrometry.
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Project description:Protein palmitoylation has been shown to be an important post-translational modification in eukaryotic cells. This modification alters the localization and/or the function of the targeted protein. In recent years, protein palmitoylation has risen in importance in apicomplexan parasites as well. In Toxoplasma gondii, some proteins have been reported to be modified by palmitate. With the development of new techniques that allow the isolation of palmitoylated proteins, this significant post-translational modification has begun to be studied in more detail in T. gondii. Here we describe the palmitoylome of the tachyzoite stage of T. gondii using a combination of the acyl-biotin exchange chemistry method and mass spectrometry analysis. We identified 401 proteins found in multiple cellular compartments, with a wide range of functions that vary from metabolic processes, gliding and host-cell invasion to even regulation of transcription and translation. Besides, we found that more rhoptry proteins than the ones already described for Toxoplasma are palmitoylated, suggesting an important role for this modification in the invasion mechanism of the host-cell. This study documents that protein palmitoylation is a common modification in T. gondii that could have an impact on different cellular processes.
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