Dual-Luciferase-Based Fast and Sensitive Detection of Malaria Hypnozoites for the Discovery of Antirelapse Compounds
Efforts to eradicate Plasmodium vivax malaria are hampered by the presence of hypnozoites, persisting stages in the liver that can reactivate after prolonged periods of time enabling further transmission and causing renewed disease. Large-scale drug screening is needed to identify compounds with ant...
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| Veröffentlicht in: | Analytical chemistry (Washington) 2020-05, Vol.92 (9), p.6667-6675 |
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| creator | Voorberg-van der Wel, Annemarie M Zeeman, Anne-Marie Nieuwenhuis, Ivonne G van der Werff, Nicole M Klooster, Els J Klop, Onny Vermaat, Lars C Kocken, Clemens H. M |
| description | Efforts to eradicate Plasmodium vivax malaria are hampered by the presence of hypnozoites, persisting stages in the liver that can reactivate after prolonged periods of time enabling further transmission and causing renewed disease. Large-scale drug screening is needed to identify compounds with antihypnozoite activity, but current platforms rely on time-consuming high-content fluorescence imaging as read-out, limiting assay throughput. We here report an ultrafast and sensitive dual-luciferase-based method to differentiate hypnozoites from liver stage schizonts using a transgenic P. cynomolgi parasite line that contains Nanoluc driven by the constitutive hsp70 promoter, as well as firefly luciferase driven by the schizont-specific lisp2 promoter. The transgenic parasite line showed similar fitness and drug sensitivity profiles of selected compounds to wild type. We demonstrate robust bioluminescence-based detection of hypnozoites in 96-well and 384-well plate formats, setting the stage for implementation in large scale drug screens. |
| doi_str_mv | 10.1021/acs.analchem.0c00547 |
| format | Article |
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The transgenic parasite line showed similar fitness and drug sensitivity profiles of selected compounds to wild type. We demonstrate robust bioluminescence-based detection of hypnozoites in 96-well and 384-well plate formats, setting the stage for implementation in large scale drug screens.</description><identifier>ISSN: 0003-2700</identifier><identifier>EISSN: 1520-6882</identifier><identifier>DOI: 10.1021/acs.analchem.0c00547</identifier><identifier>PMID: 32267675</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Analytical chemistry ; Animals ; Antimalarials - pharmacology ; Bioluminescence ; Cells, Cultured ; Chemistry ; Disease transmission ; Drug Discovery ; Drug screening ; Fluorescence ; Hepatocytes - drug effects ; Hepatocytes - parasitology ; Hsp70 protein ; Liver ; Luciferases - metabolism ; Luminescent Measurements ; Macaca mulatta ; Malaria ; Malaria - diagnostic imaging ; Malaria - drug therapy ; Optical Imaging ; Parasites ; Parasitic Sensitivity Tests ; Plasmodium - drug effects ; Schizonts ; Vector-borne diseases</subject><ispartof>Analytical chemistry (Washington), 2020-05, Vol.92 (9), p.6667-6675</ispartof><rights>Copyright American Chemical Society May 5, 2020</rights><rights>Copyright © 2020 American Chemical Society 2020 American Chemical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a477t-321d739ce1d59f9c5e3392f9aed016577ed02f2fbeea702a8519625c2b90fe9d3</citedby><cites>FETCH-LOGICAL-a477t-321d739ce1d59f9c5e3392f9aed016577ed02f2fbeea702a8519625c2b90fe9d3</cites><orcidid>0000-0001-9403-0515</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.analchem.0c00547$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.analchem.0c00547$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>230,314,780,784,885,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32267675$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Voorberg-van der Wel, Annemarie M</creatorcontrib><creatorcontrib>Zeeman, Anne-Marie</creatorcontrib><creatorcontrib>Nieuwenhuis, Ivonne G</creatorcontrib><creatorcontrib>van der Werff, Nicole M</creatorcontrib><creatorcontrib>Klooster, Els J</creatorcontrib><creatorcontrib>Klop, Onny</creatorcontrib><creatorcontrib>Vermaat, Lars C</creatorcontrib><creatorcontrib>Kocken, Clemens H. M</creatorcontrib><title>Dual-Luciferase-Based Fast and Sensitive Detection of Malaria Hypnozoites for the Discovery of Antirelapse Compounds</title><title>Analytical chemistry (Washington)</title><addtitle>Anal. Chem</addtitle><description>Efforts to eradicate Plasmodium vivax malaria are hampered by the presence of hypnozoites, persisting stages in the liver that can reactivate after prolonged periods of time enabling further transmission and causing renewed disease. Large-scale drug screening is needed to identify compounds with antihypnozoite activity, but current platforms rely on time-consuming high-content fluorescence imaging as read-out, limiting assay throughput. We here report an ultrafast and sensitive dual-luciferase-based method to differentiate hypnozoites from liver stage schizonts using a transgenic P. cynomolgi parasite line that contains Nanoluc driven by the constitutive hsp70 promoter, as well as firefly luciferase driven by the schizont-specific lisp2 promoter. 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We demonstrate robust bioluminescence-based detection of hypnozoites in 96-well and 384-well plate formats, setting the stage for implementation in large scale drug screens.</description><subject>Analytical chemistry</subject><subject>Animals</subject><subject>Antimalarials - pharmacology</subject><subject>Bioluminescence</subject><subject>Cells, Cultured</subject><subject>Chemistry</subject><subject>Disease transmission</subject><subject>Drug Discovery</subject><subject>Drug screening</subject><subject>Fluorescence</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - parasitology</subject><subject>Hsp70 protein</subject><subject>Liver</subject><subject>Luciferases - metabolism</subject><subject>Luminescent Measurements</subject><subject>Macaca mulatta</subject><subject>Malaria</subject><subject>Malaria - diagnostic imaging</subject><subject>Malaria - drug therapy</subject><subject>Optical Imaging</subject><subject>Parasites</subject><subject>Parasitic Sensitivity Tests</subject><subject>Plasmodium - drug effects</subject><subject>Schizonts</subject><subject>Vector-borne diseases</subject><issn>0003-2700</issn><issn>1520-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1uEzEUhUcIRNPCGyBkiQ2bCf4Zj8cbpJK2FCmIBbC2HM81cTVjD7YnUnh6HCWNgAVe-C78nXN9dKrqFcFLgil5p01aaq8Hs4VxiQ3GvBFPqgXhFNdt19Gn1QJjzGoqML6oLlN6wJgQTNrn1QWjtBWt4Isq38x6qNezcRaiTlB_KFeP7nTKSPsefQWfXHY7QDeQwWQXPAoWfdaDjk6j-_3kw6_gMiRkQ0R5W0CXTNhB3B_Aa59dhEFPCdAqjFOYfZ9eVM-sHhK8PM2r6vvd7bfVfb3-8vHT6npd60aIXDNKesGkAdJzaaXhwJikVmroSwwuRJnUUrsB0AJT3XEiW8oN3UhsQfbsqnp_9J3mzQi9AZ-jHtQU3ajjXgXt1N8v3m3Vj7BTgmImeFcM3p4MYvg5Q8pqLOFgGLSHMCdFWSdkOVwW9M0_6EOYY-mnUA0mXUMZZ4VqjpSJIaUI9vwZgtWhVlVqVY-1qlOtRfb6zyBn0WOPBcBH4CA_L_6v5284nbP_</recordid><startdate>20200505</startdate><enddate>20200505</enddate><creator>Voorberg-van der Wel, Annemarie M</creator><creator>Zeeman, Anne-Marie</creator><creator>Nieuwenhuis, Ivonne G</creator><creator>van der Werff, Nicole M</creator><creator>Klooster, Els J</creator><creator>Klop, Onny</creator><creator>Vermaat, Lars C</creator><creator>Kocken, Clemens H. 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M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dual-Luciferase-Based Fast and Sensitive Detection of Malaria Hypnozoites for the Discovery of Antirelapse Compounds</atitle><jtitle>Analytical chemistry (Washington)</jtitle><addtitle>Anal. Chem</addtitle><date>2020-05-05</date><risdate>2020</risdate><volume>92</volume><issue>9</issue><spage>6667</spage><epage>6675</epage><pages>6667-6675</pages><issn>0003-2700</issn><eissn>1520-6882</eissn><abstract>Efforts to eradicate Plasmodium vivax malaria are hampered by the presence of hypnozoites, persisting stages in the liver that can reactivate after prolonged periods of time enabling further transmission and causing renewed disease. Large-scale drug screening is needed to identify compounds with antihypnozoite activity, but current platforms rely on time-consuming high-content fluorescence imaging as read-out, limiting assay throughput. We here report an ultrafast and sensitive dual-luciferase-based method to differentiate hypnozoites from liver stage schizonts using a transgenic P. cynomolgi parasite line that contains Nanoluc driven by the constitutive hsp70 promoter, as well as firefly luciferase driven by the schizont-specific lisp2 promoter. The transgenic parasite line showed similar fitness and drug sensitivity profiles of selected compounds to wild type. We demonstrate robust bioluminescence-based detection of hypnozoites in 96-well and 384-well plate formats, setting the stage for implementation in large scale drug screens.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>32267675</pmid><doi>10.1021/acs.analchem.0c00547</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-9403-0515</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Analytical chemistry (Washington), 2020-05, Vol.92 (9), p.6667-6675 |
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| source | MEDLINE; ACS Publications |
| subjects | Analytical chemistry Animals Antimalarials - pharmacology Bioluminescence Cells, Cultured Chemistry Disease transmission Drug Discovery Drug screening Fluorescence Hepatocytes - drug effects Hepatocytes - parasitology Hsp70 protein Liver Luciferases - metabolism Luminescent Measurements Macaca mulatta Malaria Malaria - diagnostic imaging Malaria - drug therapy Optical Imaging Parasites Parasitic Sensitivity Tests Plasmodium - drug effects Schizonts Vector-borne diseases |
| title | Dual-Luciferase-Based Fast and Sensitive Detection of Malaria Hypnozoites for the Discovery of Antirelapse Compounds |
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