scholarly journals CRISPR/Cas9-engineered inducible gametocyte producer lines as a valuable tool for Plasmodium falciparum malaria transmission research

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sylwia D. Boltryk ◽  
Armin Passecker ◽  
Arne Alder ◽  
Eilidh Carrington ◽  
Marga van de Vegte-Bolmer ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Sexual Development ◽  
Mass Production ◽  
Plasmodium Falciparum Malaria ◽  
Mosquito Vector ◽  
Parasite Transmission ◽  
Large Numbers ◽  
Molecular Investigation ◽  
Transmission Stage

AbstractThe malaria parasite Plasmodium falciparum replicates inside erythrocytes in the blood of infected humans. During each replication cycle, a small proportion of parasites commits to sexual development and differentiates into gametocytes, which are essential for parasite transmission via the mosquito vector. Detailed molecular investigation of gametocyte biology and transmission has been hampered by difficulties in generating large numbers of these highly specialised cells. Here, we engineer P. falciparum NF54 inducible gametocyte producer (iGP) lines for the routine mass production of synchronous gametocytes via conditional overexpression of the sexual commitment factor GDV1. NF54/iGP lines consistently achieve sexual commitment rates of 75% and produce viable gametocytes that are transmissible by mosquitoes. We also demonstrate that further genetic engineering of NF54/iGP parasites is a valuable tool for the targeted exploration of gametocyte biology. In summary, we believe the iGP approach developed here will greatly expedite basic and applied malaria transmission stage research.

scholarly journals CRISPR/Cas9-engineered inducible gametocyte producer lines as a novel tool for basic and applied research on Plasmodium falciparum malaria transmission stages

2020 ◽  
Author(s):  
Sylwia D. Boltryk ◽  
Armin Passecker ◽  
Arne Alder ◽  
Marga van de Vegte-Bolmer ◽  
Robert W. Sauerwein ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Applied Research ◽  
Plasmodium Falciparum Malaria ◽  
Mosquito Vector ◽  
Parasite Transmission ◽  
Large Numbers ◽  
Molecular Investigation ◽  
Invaluable Tool ◽  
Marker Free ◽  
Basic And Applied Research

AbstractThe malaria parasite Plasmodium falciparum replicates inside erythrocytes in the blood of infected humans. During each replication cycle, a small proportion of parasites commits to sexual development and differentiates into gametocytes, which are essential for parasite transmission to other human hosts via the mosquito vector. Detailed molecular investigation of gametocyte biology and transmission has been hampered by difficulties in generating large numbers of these highly specialized cells. Here, we engineered marker-free P. falciparum inducible gametocyte producer (iGP) lines for the routine mass production of synchronous gametocytes. Through targeted overexpression of the sexual commitment factor GDV1, iGP lines consistently achieve sexual commitment rates of 75% and produce gametocytes that are infectious to mosquitoes. Subsequent tagging of a nucleoporin allowed us to visualize marked nuclear transformations during gametocytogenesis and demonstrates that further genetic engineering of iGP lines is an invaluable tool for the targeted exploration of gametocyte biology. We believe the iGP approach developed here opens up unprecedented opportunities that will expedite future basic and applied research on P. falciparum transmission stages.

scholarly journals CRISPR/Cas9-engineered inducible gametocyte producer lines as a novel tool for basic and applied research on Plasmodium falciparum malaria transmission stages

2020 ◽  
Author(s):  
Sylwia Boltryk ◽  
Armin Passecker ◽  
Arne Alder ◽  
Marga van de Vegte-Bolmer ◽  
Robert Sauerwein ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Applied Research ◽  
Plasmodium Falciparum Malaria ◽  
Mosquito Vector ◽  
Large Numbers ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Invaluable Tool ◽  
Marker Free ◽  
Basic And Applied Research

Abstract The malaria parasite Plasmodium falciparum replicates inside erythrocytes in the blood of infected humans. During each replication cycle, a small proportion of parasites commits to sexual development and differentiates into gametocytes, which are essential for parasite transmission to other human hosts via the mosquito vector. Detailed molecular investigation of gametocyte biology and transmission has been hampered by difficulties in generating large numbers of these highly specialized cells. Here, we engineered marker-free P. falciparum inducible gametocyte producer (iGP) lines for the routine mass production of synchronous gametocytes. Through targeted overexpression of the sexual commitment factor GDV1, iGP lines consistently achieve sexual commitment rates of 75% and produce gametocytes that are infectious to mosquitoes. Subsequent tagging of a nucleoporin allowed us to visualize marked nuclear transformations during gametocytogenesis and demonstrates that further genetic engineering of iGP lines is an invaluable tool for the targeted exploration of gametocyte biology. We believe the iGP approach developed here opens up unprecedented opportunities that will expedite future basic and applied research on P. falciparum transmission stages.

scholarly journals Effect of naturally occurring Wolbachia in Anopheles gambiae s.l. mosquitoes from Mali on Plasmodium falciparum malaria transmission

2017 ◽  
Vol 114 (47) ◽  
pp. 12566-12571 ◽  
Author(s):  
Fabio M. Gomes ◽  
Bretta L. Hixson ◽  
Miles D. W. Tyner ◽  
Jose Luis Ramirez ◽  
Gaspar E. Canepa ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Anopheles Gambiae ◽  
Malaria Transmission ◽  
Deleterious Effect ◽  
Plasmodium Falciparum Malaria ◽  
Anopheles Coluzzii ◽  
Naturally Occurring ◽  
Anopheles Gambiae S.L ◽  
Cat Fleas ◽  
Sporozoite Infection

A naturally occurring Wolbachia strain (wAnga-Mali) was identified in mosquitoes of the Anopheles gambiae complex collected in the Malian villages of Dangassa and Kenieroba. Phylogenetic analysis of the nucleotide sequence of two 16S rRNA regions showed that wAnga-Mali clusters with Wolbachia strains from supergroup A and has the highest homology to a Wolbachia strain isolated from cat fleas (Ctenocephalides). wAnga-Mali is different from two Wolbachia strains previously reported in A. gambiae from Burkina Faso (wAnga_VK5_STP and wAnga_VK5_3.1a). Quantitative analysis of Wolbachia and Plasmodium sporozoite infection in field-collected mosquitoes indicates that the prevalence and intensity of Plasmodium falciparum sporozoite infection is significantly lower in Wolbachia-infected females. The presence of Wolbachia in females from a laboratory Anopheles coluzzii (A. gambiae, M form) colony experimentally infected with P. falciparum (NF54 strain) gametocyte cultures slightly enhanced oocyst infection. However, Wolbachia infection significantly reduced the prevalence and intensity of sporozoite infection, as observed in the field. This indicates that wAnga-Mali infection does not limit early stages of Plasmodium infection in the mosquito, but it has a strong deleterious effect on sporozoites and reduces malaria transmission.

scholarly journals Reducing Plasmodium falciparum Malaria Transmission in Africa: A Model-Based Evaluation of Intervention Strategies

PLoS Medicine ◽  
2010 ◽  
Vol 7 (8) ◽  
pp. e1000324 ◽  
Author(s):  
Jamie T. Griffin ◽  
T. Deirdre Hollingsworth ◽  
Lucy C. Okell ◽  
Thomas S. Churcher ◽  
Michael White ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Falciparum Malaria ◽  
Plasmodium Falciparum Malaria ◽  
Intervention Strategies ◽  
Model Based

scholarly journals Global & Temporal Patterns of Submicroscopic Plasmodium falciparum Malaria Infection

2019 ◽  
Author(s):  
Charles Whittaker ◽  
Hannah Slater ◽  
Teun Bousema ◽  
Chris Drakeley ◽  
Azra Ghani ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Infection ◽  
Molecular Detection ◽  
Plasmodium Falciparum Malaria ◽  
West African ◽  
South American ◽  
Cross Sectional ◽  
Large Numbers ◽  
Current Transmission ◽  
Submicroscopic Infection

AbstractMolecular detection of Plasmodium falciparum infection has revealed large numbers of individuals with low-density (yet transmissible) infections undetectable by microscopy. Here we present an updated systematic review of cross-sectional malaria surveys to explore the prevalence and drivers of these submicroscopic infections and define where they are likely to be relevant to malaria control efforts. Our results show that submicroscopic infections predominate in low transmission settings, but also reveal marked geographical variation in their prevalence, being highest in South American surveys and lowest in West African studies. Whilst current transmission levels partly explain these results, we find that historical transmission intensity also represents a crucial determinant of the size of the submicroscopic reservoir. Submicroscopic infection was more likely in adults than children, although we did not observe a statistically significant influence of seasonality. Our results suggest that the contribution of submicroscopic infections to transmission likely varies substantially across settings, potentially warranting different approaches to their targeting in the approach to elimination.

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