Generation of Transmission-Competent Human Malaria Parasites with Chromosomally-Integrated Fluorescent Reporters

Abstract Malaria parasites have a complex life cycle that includes specialized stages for transmission between their mosquito and human hosts. These stages are an understudied part of the lifecycle yet targeting them is an essential component of the effort to shrink the malaria map. The human parasi...

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Autores principales:	Kyle Jarrod McLean, Judith Straimer, Christine S. Hopp, Joel Vega-Rodriguez, Jennifer L. Small-Saunders, Sachie Kanatani, Abhai Tripathi, Godfree Mlambo, Peter C. Dumoulin, Chantal T. Harris, Xinran Tong, Melanie J. Shears, Johan Ankarklev, Björn F. C. Kafsack, David A. Fidock, Photini Sinnis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6cd4b2ab743b40668a54bf07aa368fc2
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spelling	oai:doaj.org-article:6cd4b2ab743b40668a54bf07aa368fc22021-12-02T15:09:31ZGeneration of Transmission-Competent Human Malaria Parasites with Chromosomally-Integrated Fluorescent Reporters10.1038/s41598-019-49348-x2045-2322https://doaj.org/article/6cd4b2ab743b40668a54bf07aa368fc22019-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-49348-xhttps://doaj.org/toc/2045-2322Abstract Malaria parasites have a complex life cycle that includes specialized stages for transmission between their mosquito and human hosts. These stages are an understudied part of the lifecycle yet targeting them is an essential component of the effort to shrink the malaria map. The human parasite Plasmodium falciparum is responsible for the majority of deaths due to malaria. Our goal was to generate transgenic P. falciparum lines that could complete the lifecycle and produce fluorescent transmission stages for more in-depth and high-throughput studies. Using zinc-finger nuclease technology to engineer an integration site, we generated three transgenic P. falciparum lines in which tdtomato or gfp were stably integrated into the genome. Expression was driven by either stage-specific peg4 and csp promoters or the constitutive ef1a promoter. Phenotypic characterization of these lines demonstrates that they complete the life cycle with high infection rates and give rise to fluorescent mosquito stages. The transmission stages are sufficiently bright for intra-vital imaging, flow cytometry and scalable screening of chemical inhibitors and inhibitory antibodies.Kyle Jarrod McLeanJudith StraimerChristine S. HoppJoel Vega-RodriguezJennifer L. Small-SaundersSachie KanataniAbhai TripathiGodfree MlamboPeter C. DumoulinChantal T. HarrisXinran TongMelanie J. ShearsJohan AnkarklevBjörn F. C. KafsackDavid A. FidockPhotini SinnisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kyle Jarrod McLean Judith Straimer Christine S. Hopp Joel Vega-Rodriguez Jennifer L. Small-Saunders Sachie Kanatani Abhai Tripathi Godfree Mlambo Peter C. Dumoulin Chantal T. Harris Xinran Tong Melanie J. Shears Johan Ankarklev Björn F. C. Kafsack David A. Fidock Photini Sinnis Generation of Transmission-Competent Human Malaria Parasites with Chromosomally-Integrated Fluorescent Reporters
description	Abstract Malaria parasites have a complex life cycle that includes specialized stages for transmission between their mosquito and human hosts. These stages are an understudied part of the lifecycle yet targeting them is an essential component of the effort to shrink the malaria map. The human parasite Plasmodium falciparum is responsible for the majority of deaths due to malaria. Our goal was to generate transgenic P. falciparum lines that could complete the lifecycle and produce fluorescent transmission stages for more in-depth and high-throughput studies. Using zinc-finger nuclease technology to engineer an integration site, we generated three transgenic P. falciparum lines in which tdtomato or gfp were stably integrated into the genome. Expression was driven by either stage-specific peg4 and csp promoters or the constitutive ef1a promoter. Phenotypic characterization of these lines demonstrates that they complete the life cycle with high infection rates and give rise to fluorescent mosquito stages. The transmission stages are sufficiently bright for intra-vital imaging, flow cytometry and scalable screening of chemical inhibitors and inhibitory antibodies.
format	article
author	Kyle Jarrod McLean Judith Straimer Christine S. Hopp Joel Vega-Rodriguez Jennifer L. Small-Saunders Sachie Kanatani Abhai Tripathi Godfree Mlambo Peter C. Dumoulin Chantal T. Harris Xinran Tong Melanie J. Shears Johan Ankarklev Björn F. C. Kafsack David A. Fidock Photini Sinnis
author_facet	Kyle Jarrod McLean Judith Straimer Christine S. Hopp Joel Vega-Rodriguez Jennifer L. Small-Saunders Sachie Kanatani Abhai Tripathi Godfree Mlambo Peter C. Dumoulin Chantal T. Harris Xinran Tong Melanie J. Shears Johan Ankarklev Björn F. C. Kafsack David A. Fidock Photini Sinnis
author_sort	Kyle Jarrod McLean
title	Generation of Transmission-Competent Human Malaria Parasites with Chromosomally-Integrated Fluorescent Reporters
title_short	Generation of Transmission-Competent Human Malaria Parasites with Chromosomally-Integrated Fluorescent Reporters
title_full	Generation of Transmission-Competent Human Malaria Parasites with Chromosomally-Integrated Fluorescent Reporters
title_fullStr	Generation of Transmission-Competent Human Malaria Parasites with Chromosomally-Integrated Fluorescent Reporters
title_full_unstemmed	Generation of Transmission-Competent Human Malaria Parasites with Chromosomally-Integrated Fluorescent Reporters
title_sort	generation of transmission-competent human malaria parasites with chromosomally-integrated fluorescent reporters
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/6cd4b2ab743b40668a54bf07aa368fc2
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Generation of Transmission-Competent Human Malaria Parasites with Chromosomally-Integrated Fluorescent Reporters

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