scholarly journals Bioinformatics analysis of calcium-dependent protein kinase 4 (CDPK4) as Toxoplasma gondii vaccine target

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Masoud Foroutan ◽  
Ali Dalir Ghaffari ◽  
Shahrzad Soltani ◽  
Hamidreza Majidiani ◽  
Ali Taghipour ◽  
...  
Keyword(s):  
Amino Acid ◽  
Toxoplasma Gondii ◽  
Average Molecular Weight ◽  
Alpha Helix ◽  
Effective Vaccine ◽  
Amino Acid Residues ◽  
T Cell Epitopes ◽  
Calcium Dependent ◽  
Aliphatic Index ◽  
Dependent Protein

Abstract Objectives Toxoplasma gondii (T. gondii), an obligate intracellular apicomplexan parasite, could affect numerous warm-blooded animals, such as humans. Calcium-dependent protein kinases (CDPKs) are essential Ca2+ signaling mediators and participate in parasite host cell egress, outer membrane motility, invasion, and cell division. Results Several bioinformatics online servers were employed to analyze and predict the important properties of CDPK4 protein. The findings revealed that CDPK4 peptide has 1158 amino acid residues with average molecular weight (MW) of 126.331 KDa. The aliphatic index and GRAVY for this protein were estimated at 66.82 and – 0.650, respectively. The findings revealed that the CDPK4 protein comprised 30.14% and 34.97% alpha-helix, 59.84% and 53.54% random coils, and 10.02% and 11.49% extended strand with SOPMA and GOR4 tools, respectively. Ramachandran plot output showed 87.87%, 8.40%, and 3.73% of amino acid residues in the favored, allowed, and outlier regions, respectively. Also, several potential B and T-cell epitopes were predicted for CDPK4 protein through different bioinformatics tools. Also, antigenicity and allergenicity evaluation demonstrated that this protein has immunogenic and non-allergenic nature. This paper presents a basis for further studies, thereby provides a fundamental basis for the development of an effective vaccine against T. gondii infection.

scholarly journals Immunoinformatic Analysis of Calcium-Dependent Protein Kinase 7 (CDPK7) Showed Potential Targets for Toxoplasma gondii Vaccine

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Ali Taghipour ◽  
Sanaz Tavakoli ◽  
Mohamad Sabaghan ◽  
Masoud Foroutan ◽  
Hamidreza Majidiani ◽  
...  
Keyword(s):  
Amino Acid ◽  
Toxoplasma Gondii ◽  
Average Molecular Weight ◽  
Alpha Helix ◽  
Host Cells ◽  
Amino Acid Residues ◽  
Calcium Dependent ◽  
Grand Average ◽  
Dependent Protein ◽  
Basic Features

Apicomplexan parasites, including Toxoplasma gondii (T. gondii), express different types of calcium-dependent protein kinases (CDPKs), which perform a variety of functions, including attacking and exiting the host cells. In the current bioinformatics study, we have used several web servers to predict the basic features and specifications of the CDPK7 protein. The findings showed that CDPK7 protein has 2133 amino acid residues with an average molecular weight (MW) of 219085.79 D. The aliphatic index with 68.78 and grand average of hydropathicity (GRAVY) with -0.331 score were estimated. The outcomes of current research showed that the CDPK7 protein included 502 alpha-helix, 1311 random coils, and 320 extended strands with GOR4 method. Considering the Ramachandran plot, the favored region contains more than 92% of the amino acid residues. In addition, evaluation of antigenicity and allergenicity showed that CDPK7 protein has immunogenic and nonallergenic nature. The present research provides key data for more animal-model study on the CDPK7 protein to design an efficient vaccine against toxoplasmosis in the future.

scholarly journals A Novel Calcium-Dependent Protein Kinase 1 Inhibitor Potently Prevents Toxoplasma gondii Transmission to Foetuses in Mouse

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4203
Author(s):  
Héloïse Débare ◽  
Nathalie Moiré ◽  
Firmin Baron ◽  
Louis Lantier ◽  
Bruno Héraut ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Toxoplasma Gondii ◽  
Intraperitoneal Administration ◽  
Congenital Toxoplasmosis ◽  
Parasite Burden ◽  
Oral Route ◽  
Dependent Protein Kinase ◽  
Calcium Dependent ◽  
Dependent Protein ◽  
Calcium Dependent Protein Kinase

Treatments currently used to prevent congenital toxoplasmosis are non-specific of Toxoplasma gondii and have grievous side effects. To develop a more specific and less toxic drug, we have designed SP230, an imidazo[1,2-b]pyridazine salt targeting the Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) and active against acute toxoplasmosis in mice. Efficiency of SP230 to inhibit foetal transmission of the parasite was evaluated in a mouse model of congenital toxoplasmosis. Swiss mice were infected at mid-pregnancy with tachyzoites or cysts of the ME49 strain of T. gondii by intraperitoneal and oral route, respectively, and treated with SP230 at 50 mg/kg for 5 days by the same routes. Parasite burden in organs of dams and in foetuses was measured by quantitative PCR. Intraperitoneal administration of SP230 drastically reduced the number of parasites (more than 97% of reduction) in the brain and lungs of dams, and led to a reduction of 66% of parasite burden in foetuses. Oral administration of SP230 was particularly efficient with 97% of reduction of parasite burdens in foetuses. SP230 did not impact number and weight of offspring in our conditions. This inhibitor of TgCDPK1 is a promising candidate for the development of alternative therapeutics to treat infected pregnant women.

scholarly journals In Silico Prediction of T and B Cell Epitopes of SAG1-Related Sequence 3 (SRS3) Gene for Developing Toxoplasma gondii Vaccine

2020 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Abolfazl Mirzadeh ◽  
Geita Saadatnia ◽  
Majid Golkar ◽  
Jalal Babaie ◽  
Samira Amiri ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Dna Vaccine ◽  
In Silico ◽  
Effective Vaccine ◽  
T Cell Epitopes ◽  
In Silico Prediction ◽  
Vaccine Strategy ◽  
Related Sequence ◽  
Ideal Tool ◽  
Major Surface

: Toxoplasmosis is a worldwide infection that can lead to serious problems in immune-compromised individuals and fetuses. A DNA vaccine strategy would be an ideal tool against Toxoplasma gondii. One of the necessary measures to provide an effective vaccine is the selection of proteins with high antigenicity. The SAG1-related sequence 3 (SRS3) protein is a major surface antigen in T. gondii that can be used as a vaccine candidate. In the present study, bioinformatics and computational methods were utilized to predict protein characteristics, as well as secondary and tertiary structures. The in silico approach is highly suited to analyze, design, and evaluate DNA vaccine strategies. Hence, in silico prediction was used to identify B and T cell epitopes and compare the antigenicity of SRS3 and other candidate genes of Toxoplasma previously applied in the production of vaccines. The results of the analysis theoretically showed that SRS3 has multiple epitopes with high antigenicity, proposing that SRS3 is a promising immunogenic candidate for the development of DNA vaccines against toxoplasmosis.

scholarly journals Analysis of Noncanonical Calcium-Dependent Protein Kinases in Toxoplasma gondii by Targeted Gene Deletion Using CRISPR/Cas9

2016 ◽  
Vol 84 (5) ◽  
pp. 1262-1273 ◽  
Author(s):  
Shaojun Long ◽  
Qiuling Wang ◽  
L. David Sibley
Keyword(s):  
Toxoplasma Gondii ◽  
Protein Kinases ◽  
Gene Deletion ◽  
Cyst Formation ◽  
Content Type ◽  
Calcium Dependent ◽  
Targeted Gene Deletion ◽  
Dependent Protein ◽  
Calcium Dependent Protein Kinases

Calcium-dependent protein kinases (CDPKs) are expanded in apicomplexan parasites, especially inToxoplasma gondiiwhere 14 separate genes encoding these enzymes are found. Although previous studies have shown that several CDPKs play a role in controlling invasion, egress, and cell division inT. gondii, the roles of most of these genes are unexplored. Here we developed a more efficient method for gene disruption using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) that was modified to completely delete large, multiexonic genes from the genome and to allow serial replacement by recycling of the selectable marker using Cre-loxP. Using this system, we generated a total of 24 mutants in type 1 and 2 genetic backgrounds to ascertain the functions of noncanonical CDPKs. Remarkably, although we were able to confirm the essentiality of CDPK1 and CDPK7, the majority of CDPKs had no discernible phenotype for growthin vitroor infection in the mouse model. The exception to this was CDPK6, loss of which leads to reduced plaquing, fitness defect in a competition assay, and reduced tissue cyst formation in chronically infected mice. Our findings highlight the utility of CRISPR/Cas9 for rapid serial gene deletion and also suggest that additional models are needed to reveal the functions of many genes inT. gondii.

scholarly journals Thyrotropin-Receptor and Thyroid Peroxidase-Specific T Cell Clones and Their Cytokine Profile in Autoimmune Thyroid Disease1

1997 ◽  
Vol 82 (11) ◽  
pp. 3655-3663
Author(s):  
Maria Elena Fisfalen ◽  
Ellen M. Palmer ◽  
Gijs A. van Seventer ◽  
Keyoumars Soltani ◽  
Yoshikuni Sawai ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Thyroid Tissue ◽  
Cytokine Profile ◽  
Thyroid Peroxidase ◽  
Amino Acid Residues ◽  
T Cell Epitopes ◽  
T Cell Clones ◽  
Cell Clones ◽  
Ifn Γ

We studied the cytokine profile and the immune responses to thyroid antigens of specific T cell clones (TCC) isolated from patients with Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). Antigen-specific TCC were reactive to thyroid peroxidase (TPO), thyroglobulin (Tg) or human recombinant TSH-receptor extracellular domain (TSH-R), and/or their respective peptides. Of the 43 clones derived from HT patients, 65% were reactive to TPO, and 59% of the 32 clones derived from GD patients were reactive to TSH-R. TPO epitopes 100–119 and 625–644 were recognized by 75% of HT-derived clones, whereas TSH-R epitopes 158–176, 207–222, and 343–362/357–376 were recognized by 85% of GD-derived TCC. The TCC were classified according to their cytokine profile into T helper cell (Th)0 [secreting interleukin (IL)-4, IL-5, interferon (IFN)-γ], Th1 (secreting IFN-γ) and Th2 (secreting IL-4 and/or IL-5). Tumor necrosis factor-β and IL-10 were produced by all subsets. The specific TCC were predominantly Th1-like cells in HT, and were Th0- and Th1-like cells in GD. Fifty three percent of Th0 clones were derived from GD patients and were reactive to TSH-R, whereas 50% of Th1 clones were derived from HT patients and were reactive to TPO or Tg. Most Th2 clones (82%) were reactive to TPO and were established from peripheral blood. All these clones produced IL-5, and 64% produced IL-4 and IL-10. Interestingly, IFN-γ was highly produced by TPO- or Tg-specific clones established from HT thyroid tissue. These results confirm at the clonal level our previous studies regarding T cell epitopes on TPO and TSH-R molecules and support the concept that immunodominant T cell epitopes are located on amino acid residues 100–119 and 625–644 of TPO in HT and amino acid residues 158–176, 207–222 and 343–362/357–376 of TSH-R in GD. Our studies also demonstrate that thyroid-specific T cells can be classified into Th0, Th1, and Th2 subsets. TPO- or Tg-specific clones with Th1 phenotype appear to be involved in the pathogenesis of HT, mediating thyroid tissue destruction, whereas TSH-R clones with Th0 phenotype may induce thyroid-stimulating autoantibodies in GD.

scholarly journals Optimizing Small Molecule Inhibitors of Calcium-Dependent Protein Kinase 1 to Prevent Infection by Toxoplasma gondii

2013 ◽  
Vol 56 (7) ◽  
pp. 3068-3077 ◽  
Author(s):  
Sebastian Lourido ◽  
Chao Zhang ◽  
Michael S. Lopez ◽  
Keliang Tang ◽  
Jennifer Barks ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Toxoplasma Gondii ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Dependent Protein Kinase ◽  
Calcium Dependent ◽  
Dependent Protein ◽  
Calcium Dependent Protein Kinase
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