| Autor: |
Roshan Sivakumar, Katherine Floyd, Jessey Erath, Alex Jacoby, Jenny Kim Kim, Peter O. Bayguinov, James A. J. Fitzpatrick, Dennis Goldfarb, Marko Jovanovic, Abhai Tripathi, Sergej Djuranovic, Slavica Pavlovic-Djuranovic |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Malaria Journal, Vol 23, Iss 1, Pp 1-18 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1475-2875 |
| DOI: |
10.1186/s12936-024-05056-0 |
| Popis: |
Abstract Background Plasmodium falciparum, the malaria-causing parasite, is a leading cause of infection-induced deaths worldwide. The preferred treatment approach is artemisinin-based combination therapy, which couples fast-acting artemisinin derivatives with longer-acting drugs, such as lumefantrine, mefloquine, and amodiaquine. However, the urgency for new treatments has risen due to the parasite's growing resistance to existing therapies. In this study, a common characteristic of the P. falciparum proteome—stretches of poly-lysine residues, such as those found in proteins related to adhesion and pathogenicity—is investigated for its potential to treat infected erythrocytes. Methods This study utilizes in vitro culturing of intra-erythrocytic P. falciparum to assess the ability of poly-lysine peptides to inhibit the parasite’s growth, measured via flow cytometry of acridine orange-stained infected erythrocytes. The inhibitory effect of many poly-lysine lengths and modifications were tested this way. Affinity pull-downs and mass spectrometry were performed to identify the proteins interacting with these poly-lysines. Results A single dose of these poly-basic peptides can successfully diminish parasitemia in human erythrocytes in vitro with minimal toxicity. The effectiveness of the treatment correlates with the length of the poly-lysine peptide, with 30 lysine peptides supporting the eradication of erythrocytic parasites within 72 h. PEG-ylation of the poly-lysine peptides or utilizing poly-lysine dendrimers and polymers retains or increases parasite clearance efficiency and bolsters the stability of these potential new therapeutics. Lastly, affinity pull-downs and mass-spectrometry identify P. falciparum’s outer membrane proteins as likely targets for polybasic peptide medications. Conclusion Since poly-lysine dendrimers are already FDA-approved for drug delivery and this study displays their potency against intraerythrocytic P. falciparum, their adaptation as anti-malarial drugs presents a promising new therapeutic strategy for malaria. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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