Secreted Trypanosome Cyclophilin Inactivates Lytic Insect Defense Peptides and Induces Parasite Calcineurin Activation and Infectivity
The mechanisms by which <i>Trypanosoma cruzi</i> survives antimicrobial peptides and differentiates during its transit through the gastrointestinal tract of the reduviid vector are unknown. We show that cyclophilin, a peptidyl-prolyl isomerase secreted from <i>T. cruzi</i> epimastigotes, binds to an...
| Main Authors: | , , , , , |
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| Format: | Journal Article |
| Language: | Inglés |
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Elsevier
2013
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10568/129407 |
| _version_ | 1855531344102162432 |
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| author | Kulkarni, Manjusha M. Karafova, Anna Kamysz, Wojciech Schenkman, Sergio Pellé, Roger McGwire, Bradford S. |
| author_browse | Kamysz, Wojciech Karafova, Anna Kulkarni, Manjusha M. McGwire, Bradford S. Pellé, Roger Schenkman, Sergio |
| author_facet | Kulkarni, Manjusha M. Karafova, Anna Kamysz, Wojciech Schenkman, Sergio Pellé, Roger McGwire, Bradford S. |
| author_sort | Kulkarni, Manjusha M. |
| collection | Repository of Agricultural Research Outputs (CGSpace) |
| description | The mechanisms by which <i>Trypanosoma cruzi</i> survives antimicrobial peptides and differentiates during its transit through the gastrointestinal tract of the reduviid vector are unknown. We show that cyclophilin, a peptidyl-prolyl isomerase secreted from <i>T. cruzi</i> epimastigotes, binds to and neutralizes the reduviid antimicrobial peptide trialysin promoting parasite survival. This is dependent on a singular proline residue in trialysin and is inhibited by the cyclophilin inhibitor cyclosporine A. In addition, cyclophilin-trialysin complexes enhance the production of ATP and reductase responses of parasites, which are inhibited by both calcineurin-specific inhibitors cyclosporine A and FK506. Calcineurin phosphatase activity of cyclophilin-trialysin-treated parasites was higher than in controls and was inhibited by preincubation by either inhibitor. Parasites exposed to cyclophilin-trialysin have enhanced binding and invasion of host cells leading to higher infectivity. Leishmanial cyclophilin also mediates trialysin protection and metabolic stimulation by <i>T. cruzi</i>, indicating that extracellular cyclophilin may be critical to adaptation in other insect-borne protozoa. This work demonstrates that cyclophilin serves as molecular sensor leading to the evasion and adaptive metabolic response to insect defense peptides. |
| format | Journal Article |
| id | CGSpace129407 |
| institution | CGIAR Consortium |
| language | Inglés |
| publishDate | 2013 |
| publishDateRange | 2013 |
| publishDateSort | 2013 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| record_format | dspace |
| spelling | CGSpace1294072025-12-08T09:54:28Z Secreted Trypanosome Cyclophilin Inactivates Lytic Insect Defense Peptides and Induces Parasite Calcineurin Activation and Infectivity Kulkarni, Manjusha M. Karafova, Anna Kamysz, Wojciech Schenkman, Sergio Pellé, Roger McGwire, Bradford S. peptides parasite infectivity The mechanisms by which <i>Trypanosoma cruzi</i> survives antimicrobial peptides and differentiates during its transit through the gastrointestinal tract of the reduviid vector are unknown. We show that cyclophilin, a peptidyl-prolyl isomerase secreted from <i>T. cruzi</i> epimastigotes, binds to and neutralizes the reduviid antimicrobial peptide trialysin promoting parasite survival. This is dependent on a singular proline residue in trialysin and is inhibited by the cyclophilin inhibitor cyclosporine A. In addition, cyclophilin-trialysin complexes enhance the production of ATP and reductase responses of parasites, which are inhibited by both calcineurin-specific inhibitors cyclosporine A and FK506. Calcineurin phosphatase activity of cyclophilin-trialysin-treated parasites was higher than in controls and was inhibited by preincubation by either inhibitor. Parasites exposed to cyclophilin-trialysin have enhanced binding and invasion of host cells leading to higher infectivity. Leishmanial cyclophilin also mediates trialysin protection and metabolic stimulation by <i>T. cruzi</i>, indicating that extracellular cyclophilin may be critical to adaptation in other insect-borne protozoa. This work demonstrates that cyclophilin serves as molecular sensor leading to the evasion and adaptive metabolic response to insect defense peptides. 2013-03 2023-03-10T14:34:36Z 2023-03-10T14:34:36Z Journal Article https://hdl.handle.net/10568/129407 en Open Access Elsevier Kulkarni, Manjusha M.; Karafova, Anna; Kamysz, Wojciech; Schenkman, Sergio; Pellé, Roger; McGwire, Bradford S. 2013. Secreted Trypanosome Cyclophilin Inactivates Lytic Insect Defense Peptides and Induces Parasite Calcineurin Activation and Infectivity. Journal of Biological Chemistry 288: 8772-8784 |
| spellingShingle | peptides parasite infectivity Kulkarni, Manjusha M. Karafova, Anna Kamysz, Wojciech Schenkman, Sergio Pellé, Roger McGwire, Bradford S. Secreted Trypanosome Cyclophilin Inactivates Lytic Insect Defense Peptides and Induces Parasite Calcineurin Activation and Infectivity |
| title | Secreted Trypanosome Cyclophilin Inactivates Lytic Insect Defense Peptides and Induces Parasite Calcineurin Activation and Infectivity |
| title_full | Secreted Trypanosome Cyclophilin Inactivates Lytic Insect Defense Peptides and Induces Parasite Calcineurin Activation and Infectivity |
| title_fullStr | Secreted Trypanosome Cyclophilin Inactivates Lytic Insect Defense Peptides and Induces Parasite Calcineurin Activation and Infectivity |
| title_full_unstemmed | Secreted Trypanosome Cyclophilin Inactivates Lytic Insect Defense Peptides and Induces Parasite Calcineurin Activation and Infectivity |
| title_short | Secreted Trypanosome Cyclophilin Inactivates Lytic Insect Defense Peptides and Induces Parasite Calcineurin Activation and Infectivity |
| title_sort | secreted trypanosome cyclophilin inactivates lytic insect defense peptides and induces parasite calcineurin activation and infectivity |
| topic | peptides parasite infectivity |
| url | https://hdl.handle.net/10568/129407 |
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