Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/1089
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dc.contributor.authorSingh, Agam P. Singh-
dc.contributor.authorHada, Rahul S-
dc.contributor.authorGarg, Swati-
dc.contributor.authorShivappagowdar, Abhishek-
dc.contributor.authorBathula, Chandramohan-
dc.contributor.authorAyana, Rajagopal-
dc.contributor.authorPati, Soumya-
dc.contributor.authorKalia, Inderjeet-
dc.contributor.authorSingh, Shailja-
dc.contributor.authorSen, Subhabrata-
dc.date.accessioned2020-07-27T09:32:57Z-
dc.date.available2020-07-27T09:32:57Z-
dc.date.issued2020-03-
dc.identifier.urihttp://hdl.handle.net/123456789/1089-
dc.description.abstractThe pore forming Plasmodium Perforin Like Proteins (PPLP), expressed in all stages of the parasite life cycle are critical for completion of the parasite life cycle. The high sequence similarity in the central Membrane Attack Complex/ Perforin (MACPF) domain among PLPs and their distinct functional overlaps define them as lucrative target for developing multi-stage antimalarial therapeutics. Herein, we evaluated the mechanism of Pan-active MACPF Domain (PMD), a centrally located and highly conserved region of PPLPs, and deciphered the inhibitory potential of specifically designed PMD inhibitors. The E. coli expressed rPMD interacts with erythrocyte membrane and form pores of ~10.5 nm height and ~24.3 nm diameter leading to hemoglobin release and dextran uptake. The treatment with PMD induced erythrocytes senescence which can be hypothesized to account for the physiological effect of disseminated PLPs in loss of circulating erythrocytes inducing malaria anemia. The anti-PMD inhibitors effectively blocked intraerythrocytic growth by suppressing invasion and egress processes and protected erythrocytes against rPMD induced senescence. Moreover, these inhibitors also blocked the hepatic stage and transmission stage parasite development suggesting multi-stage, transmission-blocking potential of these inhibitors. Concievably, our study has introduced a novel set of anti-PMD inhibitors with pan-inhibitory activity against all the PPLPs members which can be developed into potent cross-stage antimalarial therapeutics along with erythrocyte senescence protective potential to occlude PPLPs mediated anemia in severe malaria.en_US
dc.language.isoenen_US
dc.publisherFrontiers Media SAen_US
dc.subjectRaman spectroscopy; anemia; atomic force microscopy; egress; erythrocyte; invasion; malaria; perforin like proteins.en_US
dc.titlePlasmodium Perforin-Like Protein Pores on the Host Cell Membrane Contribute in Its Multistage Growth and Erythrocyte Senescenceen_US
dc.journalFront Cell Infect Microbiolen_US
dc.volumeno10en_US
dc.pages121en_US
Appears in Collections:Infectious Disease, Publications

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