Targeted repression of Plasmodium apicortin by host microRNA impairs malaria parasite growth and invasion
Mature human erythrocytes contain a rich pool of microRNAs (miRNAs), which result from differentiation of the erythrocytes during the course of haematopoiesis. Recent studies have described the effect of erythrocytic miRNAs on the invasion and growth of the malaria parasite Plasmodium falciparum dur...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2020-06-01
|
| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/13/6/dmm042820 |
| _version_ | 1819277966334492672 |
|---|---|
| author | Malabika Chakrabarti Swati Garg Ayana Rajagopal Soumya Pati Shailja Singh |
| author_facet | Malabika Chakrabarti Swati Garg Ayana Rajagopal Soumya Pati Shailja Singh |
| author_sort | Malabika Chakrabarti |
| collection | DOAJ |
| description | Mature human erythrocytes contain a rich pool of microRNAs (miRNAs), which result from differentiation of the erythrocytes during the course of haematopoiesis. Recent studies have described the effect of erythrocytic miRNAs on the invasion and growth of the malaria parasite Plasmodium falciparum during the asexual blood stage of its life cycle. In this work, we have identified two erythrocytic miRNAs, miR-150-3p and miR-197-5p, that show favourable in silico hybridization with Plasmodium apicortin, a protein with putative microtubule-stabilizing properties. Co-expression of P. falciparum apicortin and these two miRNAs in a cell line model resulted in downregulation of apicortin at both the RNA and protein level. To create a disease model of erythrocytes containing miRNAs, chemically synthesized mimics of miR-150-3p and miR-197-5p were loaded into erythrocytes and subsequently used for invasion by the parasite. Growth of the parasite was hindered in miRNA-loaded erythrocytes, followed by impaired invasion; micronemal secretion was also reduced, especially in the case of miR-197-5p. Apicortin expression was found to be reduced in miRNA-loaded erythrocytes. To interpret the effect of downregulation of apicortin on parasite invasion to host erythrocytes, we investigated the secretion of the invasion-related microneme protein apical membrane antigen 1 (AMA1). AMA1 secretion was found to be reduced in miRNA-treated parasites. Overall, this study identifies apicortin as a novel target within the malaria parasite and establishes miR-197-5p as its miRNA inhibitor. This miRNA represents an unconventional nucleotide-based therapeutic and provides a new host factor-inspired strategy for the design of antimalarial molecular medicine. This article has an associated First Person interview with the first author of the paper. |
| first_indexed | 2024-12-24T00:04:30Z |
| format | Article |
| id | doaj.art-2c461a8f7bc44149a7549c99d96dc491 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-24T00:04:30Z |
| publishDate | 2020-06-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-2c461a8f7bc44149a7549c99d96dc4912022-12-21T17:25:03ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112020-06-0113610.1242/dmm.042820042820Targeted repression of Plasmodium apicortin by host microRNA impairs malaria parasite growth and invasionMalabika Chakrabarti0Swati Garg1Ayana Rajagopal2Soumya Pati3Shailja Singh4 Host Parasite Interactions and Disease Modeling Lab, Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India Host Parasite Interactions and Disease Modeling Lab, Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India Animal Physiology and Neurobiology, Katholieke Universiteit Leuven, Naamsestraat 59 - Box 2465, Belgium Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Gautam Budh Nagar, Noida, UP 201314, India Host Parasite Interactions and Disease Modeling Lab, Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India Mature human erythrocytes contain a rich pool of microRNAs (miRNAs), which result from differentiation of the erythrocytes during the course of haematopoiesis. Recent studies have described the effect of erythrocytic miRNAs on the invasion and growth of the malaria parasite Plasmodium falciparum during the asexual blood stage of its life cycle. In this work, we have identified two erythrocytic miRNAs, miR-150-3p and miR-197-5p, that show favourable in silico hybridization with Plasmodium apicortin, a protein with putative microtubule-stabilizing properties. Co-expression of P. falciparum apicortin and these two miRNAs in a cell line model resulted in downregulation of apicortin at both the RNA and protein level. To create a disease model of erythrocytes containing miRNAs, chemically synthesized mimics of miR-150-3p and miR-197-5p were loaded into erythrocytes and subsequently used for invasion by the parasite. Growth of the parasite was hindered in miRNA-loaded erythrocytes, followed by impaired invasion; micronemal secretion was also reduced, especially in the case of miR-197-5p. Apicortin expression was found to be reduced in miRNA-loaded erythrocytes. To interpret the effect of downregulation of apicortin on parasite invasion to host erythrocytes, we investigated the secretion of the invasion-related microneme protein apical membrane antigen 1 (AMA1). AMA1 secretion was found to be reduced in miRNA-treated parasites. Overall, this study identifies apicortin as a novel target within the malaria parasite and establishes miR-197-5p as its miRNA inhibitor. This miRNA represents an unconventional nucleotide-based therapeutic and provides a new host factor-inspired strategy for the design of antimalarial molecular medicine. This article has an associated First Person interview with the first author of the paper.http://dmm.biologists.org/content/13/6/dmm042820mir-150-3pmir-197-5papicortinhybridizationmicroneme secretionama1malariainvasionplasmodiumerythrocytes |
| spellingShingle | Malabika Chakrabarti Swati Garg Ayana Rajagopal Soumya Pati Shailja Singh Targeted repression of Plasmodium apicortin by host microRNA impairs malaria parasite growth and invasion Disease Models & Mechanisms mir-150-3p mir-197-5p apicortin hybridization microneme secretion ama1 malaria invasion plasmodium erythrocytes |
| title | Targeted repression of Plasmodium apicortin by host microRNA impairs malaria parasite growth and invasion |
| title_full | Targeted repression of Plasmodium apicortin by host microRNA impairs malaria parasite growth and invasion |
| title_fullStr | Targeted repression of Plasmodium apicortin by host microRNA impairs malaria parasite growth and invasion |
| title_full_unstemmed | Targeted repression of Plasmodium apicortin by host microRNA impairs malaria parasite growth and invasion |
| title_short | Targeted repression of Plasmodium apicortin by host microRNA impairs malaria parasite growth and invasion |
| title_sort | targeted repression of plasmodium apicortin by host microrna impairs malaria parasite growth and invasion |
| topic | mir-150-3p mir-197-5p apicortin hybridization microneme secretion ama1 malaria invasion plasmodium erythrocytes |
| url | http://dmm.biologists.org/content/13/6/dmm042820 |
| work_keys_str_mv | AT malabikachakrabarti targetedrepressionofplasmodiumapicortinbyhostmicrornaimpairsmalariaparasitegrowthandinvasion AT swatigarg targetedrepressionofplasmodiumapicortinbyhostmicrornaimpairsmalariaparasitegrowthandinvasion AT ayanarajagopal targetedrepressionofplasmodiumapicortinbyhostmicrornaimpairsmalariaparasitegrowthandinvasion AT soumyapati targetedrepressionofplasmodiumapicortinbyhostmicrornaimpairsmalariaparasitegrowthandinvasion AT shailjasingh targetedrepressionofplasmodiumapicortinbyhostmicrornaimpairsmalariaparasitegrowthandinvasion |