A brain cyst load-associated antigen is a Toxoplasma gondii biomarker for serodetection of persistent parasites and chronic infection
Abstract Background Biomarker discovery remains a major challenge for predictive medicine, in particular, in the context of chronic diseases. This is true for the widespread protozoan Toxoplasma gondii which establishes long-lasting parasitism in metazoans, humans included. This microbe successively...
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| Format: | Article |
| Language: | English |
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BMC
2021-02-01
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| Series: | BMC Biology |
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| Online Access: | https://doi.org/10.1186/s12915-021-00959-9 |
| _version_ | 1819178229975482368 |
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| author | Céline Dard Christopher Swale Marie-Pierre Brenier-Pinchart Dayana C. Farhat Valeria Bellini Marie Gladys Robert Dominique Cannella Hervé Pelloux Isabelle Tardieux Mohamed-Ali Hakimi |
| author_facet | Céline Dard Christopher Swale Marie-Pierre Brenier-Pinchart Dayana C. Farhat Valeria Bellini Marie Gladys Robert Dominique Cannella Hervé Pelloux Isabelle Tardieux Mohamed-Ali Hakimi |
| author_sort | Céline Dard |
| collection | DOAJ |
| description | Abstract Background Biomarker discovery remains a major challenge for predictive medicine, in particular, in the context of chronic diseases. This is true for the widespread protozoan Toxoplasma gondii which establishes long-lasting parasitism in metazoans, humans included. This microbe successively unfolds distinct genetic programs that direct the transition from high to low replicative potential inside host cells. As a slow-replicating cell, the T. gondii bradyzoite developmental stage persists enclosed in a cyst compartment within tissues including the nervous system, being held by a sustained immune equilibrium which accounts for the prolonged clinically silent phase of parasitism. Serological surveys indicate that nearly one third of the human population has been exposed to T. gondii and possibly host bradyzoites. Because any disruption of the immune balance drives the reverse transition from bradyzoite to fast replicating tachyzoite and uncontrolled growth of the latter, these people are at risk for life-threatening disease. While serological tests for discriminating recent from past infection are available, there is yet no immunogenic biomarker used in the serological test to allow ascertaining the presence of persistent bradyzoites. Results Capitalizing on genetically engineered parasites induced to produce mature bradyzoites in vitro, we have identified the BCLA/MAG2 protein being restricted to the bradyzoite and the cyst envelope. Using laboratory mice as relevant T. gondii host models, we demonstrated that BCLA/MAG2 drives the generation of antibodies that recognize bradyzoite and the enveloping cyst structure. We have designed an ELISA assay based on a bacterially produced BCLA recombinant polypeptide, which was validated using a large collection of sera from mice of different genetic backgrounds and infected with bcla+ or bcla-null cystogenic and non-cystogenic T. gondii strains. To refine the design of the ELISA assay, we applied high-resolution BCLA epitope mapping and identified a specific combination of peptides and accordingly set up a selective and sensitive ELISA assay which allowed the detection of anti-BCLA/MAG2 antibodies in the sera of human patients with various forms of toxoplasmosis. Conclusions We brought proof of principle that anti-BCLA/MAG2 antibodies serve as specific and sensitive serological markers in the perspective of a combinatorial strategy for detection of persistent T. gondii parasitism. |
| first_indexed | 2024-12-22T21:39:14Z |
| format | Article |
| id | doaj.art-1908785e03664ac6b6619f432b747fd2 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-12-22T21:39:14Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-1908785e03664ac6b6619f432b747fd22022-12-21T18:11:39ZengBMCBMC Biology1741-70072021-02-0119112610.1186/s12915-021-00959-9A brain cyst load-associated antigen is a Toxoplasma gondii biomarker for serodetection of persistent parasites and chronic infectionCéline Dard0Christopher Swale1Marie-Pierre Brenier-Pinchart2Dayana C. Farhat3Valeria Bellini4Marie Gladys Robert5Dominique Cannella6Hervé Pelloux7Isabelle Tardieux8Mohamed-Ali Hakimi9Team Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Université Grenoble AlpesTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Université Grenoble AlpesTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Université Grenoble AlpesTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Université Grenoble AlpesTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Université Grenoble AlpesTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Université Grenoble AlpesTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Université Grenoble AlpesTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Université Grenoble AlpesTeam Membrane and Cell Dynamics of Host Parasite Interactions, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Université Grenoble AlpesTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Université Grenoble AlpesAbstract Background Biomarker discovery remains a major challenge for predictive medicine, in particular, in the context of chronic diseases. This is true for the widespread protozoan Toxoplasma gondii which establishes long-lasting parasitism in metazoans, humans included. This microbe successively unfolds distinct genetic programs that direct the transition from high to low replicative potential inside host cells. As a slow-replicating cell, the T. gondii bradyzoite developmental stage persists enclosed in a cyst compartment within tissues including the nervous system, being held by a sustained immune equilibrium which accounts for the prolonged clinically silent phase of parasitism. Serological surveys indicate that nearly one third of the human population has been exposed to T. gondii and possibly host bradyzoites. Because any disruption of the immune balance drives the reverse transition from bradyzoite to fast replicating tachyzoite and uncontrolled growth of the latter, these people are at risk for life-threatening disease. While serological tests for discriminating recent from past infection are available, there is yet no immunogenic biomarker used in the serological test to allow ascertaining the presence of persistent bradyzoites. Results Capitalizing on genetically engineered parasites induced to produce mature bradyzoites in vitro, we have identified the BCLA/MAG2 protein being restricted to the bradyzoite and the cyst envelope. Using laboratory mice as relevant T. gondii host models, we demonstrated that BCLA/MAG2 drives the generation of antibodies that recognize bradyzoite and the enveloping cyst structure. We have designed an ELISA assay based on a bacterially produced BCLA recombinant polypeptide, which was validated using a large collection of sera from mice of different genetic backgrounds and infected with bcla+ or bcla-null cystogenic and non-cystogenic T. gondii strains. To refine the design of the ELISA assay, we applied high-resolution BCLA epitope mapping and identified a specific combination of peptides and accordingly set up a selective and sensitive ELISA assay which allowed the detection of anti-BCLA/MAG2 antibodies in the sera of human patients with various forms of toxoplasmosis. Conclusions We brought proof of principle that anti-BCLA/MAG2 antibodies serve as specific and sensitive serological markers in the perspective of a combinatorial strategy for detection of persistent T. gondii parasitism.https://doi.org/10.1186/s12915-021-00959-9Toxoplasma gondiiToxoplasmosisBiomarkerChronic infectionSerologyRecombinant antigen |
| spellingShingle | Céline Dard Christopher Swale Marie-Pierre Brenier-Pinchart Dayana C. Farhat Valeria Bellini Marie Gladys Robert Dominique Cannella Hervé Pelloux Isabelle Tardieux Mohamed-Ali Hakimi A brain cyst load-associated antigen is a Toxoplasma gondii biomarker for serodetection of persistent parasites and chronic infection BMC Biology Toxoplasma gondii Toxoplasmosis Biomarker Chronic infection Serology Recombinant antigen |
| title | A brain cyst load-associated antigen is a Toxoplasma gondii biomarker for serodetection of persistent parasites and chronic infection |
| title_full | A brain cyst load-associated antigen is a Toxoplasma gondii biomarker for serodetection of persistent parasites and chronic infection |
| title_fullStr | A brain cyst load-associated antigen is a Toxoplasma gondii biomarker for serodetection of persistent parasites and chronic infection |
| title_full_unstemmed | A brain cyst load-associated antigen is a Toxoplasma gondii biomarker for serodetection of persistent parasites and chronic infection |
| title_short | A brain cyst load-associated antigen is a Toxoplasma gondii biomarker for serodetection of persistent parasites and chronic infection |
| title_sort | brain cyst load associated antigen is a toxoplasma gondii biomarker for serodetection of persistent parasites and chronic infection |
| topic | Toxoplasma gondii Toxoplasmosis Biomarker Chronic infection Serology Recombinant antigen |
| url | https://doi.org/10.1186/s12915-021-00959-9 |
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