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Characterization of Plasmodium developmental transcriptomes in Anopheles gambiae midgut reveals novel regulators of malaria transmission

The passage through the mosquito is a major bottleneck for malaria parasite populations and a target of interventions aiming to block disease transmission. Here, we used DNA microarrays to profile the developmental transcriptomes of the rodent malaria parasite Plasmodium berghei in vivo, in the midg...

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Autores principales: Akinosoglou, Karolina A, Bushell, Ellen S C, Ukegbu, Chiamaka Valerie, Schlegelmilch, Timm, Cho, Jee-Sun, Redmond, Seth, Sala, Katarzyna, Christophides, George K, Vlachou, Dina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371638/
https://www.ncbi.nlm.nih.gov/pubmed/25225164
http://dx.doi.org/10.1111/cmi.12363
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author Akinosoglou, Karolina A
Bushell, Ellen S C
Ukegbu, Chiamaka Valerie
Schlegelmilch, Timm
Cho, Jee-Sun
Redmond, Seth
Sala, Katarzyna
Christophides, George K
Vlachou, Dina
author_facet Akinosoglou, Karolina A
Bushell, Ellen S C
Ukegbu, Chiamaka Valerie
Schlegelmilch, Timm
Cho, Jee-Sun
Redmond, Seth
Sala, Katarzyna
Christophides, George K
Vlachou, Dina
author_sort Akinosoglou, Karolina A
collection PubMed
description The passage through the mosquito is a major bottleneck for malaria parasite populations and a target of interventions aiming to block disease transmission. Here, we used DNA microarrays to profile the developmental transcriptomes of the rodent malaria parasite Plasmodium berghei in vivo, in the midgut of Anopheles gambiae mosquitoes, from parasite stages in the midgut blood bolus to sporulating oocysts on the basal gut wall. Data analysis identified several distinct transcriptional programmes encompassing genes putatively involved in developmental processes or in interactions with the mosquito. At least two of these programmes are associated with the ookinete development that is linked to mosquito midgut invasion and establishment of infection. Targeted disruption by homologous recombination of two of these genes resulted in mutant parasites exhibiting notable infection phenotypes. GAMER encodes a short polypeptide with granular localization in the gametocyte cytoplasm and shows a highly penetrant loss-of-function phenotype manifested as greatly reduced ookinete numbers, linked to impaired male gamete release. HADO encodes a putative magnesium phosphatase with distinctive cortical localization along the concave ookinete periphery. Disruption of HADO compromises ookinete development leading to significant reduction of oocyst numbers. Our data provide important insights into the molecular framework underpinning Plasmodium development in the mosquito and identifies two genes with important functions at initial stages of parasite development in the mosquito midgut.
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spelling pubmed-43716382015-03-26 Characterization of Plasmodium developmental transcriptomes in Anopheles gambiae midgut reveals novel regulators of malaria transmission Akinosoglou, Karolina A Bushell, Ellen S C Ukegbu, Chiamaka Valerie Schlegelmilch, Timm Cho, Jee-Sun Redmond, Seth Sala, Katarzyna Christophides, George K Vlachou, Dina Cell Microbiol Original Articles The passage through the mosquito is a major bottleneck for malaria parasite populations and a target of interventions aiming to block disease transmission. Here, we used DNA microarrays to profile the developmental transcriptomes of the rodent malaria parasite Plasmodium berghei in vivo, in the midgut of Anopheles gambiae mosquitoes, from parasite stages in the midgut blood bolus to sporulating oocysts on the basal gut wall. Data analysis identified several distinct transcriptional programmes encompassing genes putatively involved in developmental processes or in interactions with the mosquito. At least two of these programmes are associated with the ookinete development that is linked to mosquito midgut invasion and establishment of infection. Targeted disruption by homologous recombination of two of these genes resulted in mutant parasites exhibiting notable infection phenotypes. GAMER encodes a short polypeptide with granular localization in the gametocyte cytoplasm and shows a highly penetrant loss-of-function phenotype manifested as greatly reduced ookinete numbers, linked to impaired male gamete release. HADO encodes a putative magnesium phosphatase with distinctive cortical localization along the concave ookinete periphery. Disruption of HADO compromises ookinete development leading to significant reduction of oocyst numbers. Our data provide important insights into the molecular framework underpinning Plasmodium development in the mosquito and identifies two genes with important functions at initial stages of parasite development in the mosquito midgut. BlackWell Publishing Ltd 2015-02 2014-10-31 /pmc/articles/PMC4371638/ /pubmed/25225164 http://dx.doi.org/10.1111/cmi.12363 Text en © 2014 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Akinosoglou, Karolina A
Bushell, Ellen S C
Ukegbu, Chiamaka Valerie
Schlegelmilch, Timm
Cho, Jee-Sun
Redmond, Seth
Sala, Katarzyna
Christophides, George K
Vlachou, Dina
Characterization of Plasmodium developmental transcriptomes in Anopheles gambiae midgut reveals novel regulators of malaria transmission
title Characterization of Plasmodium developmental transcriptomes in Anopheles gambiae midgut reveals novel regulators of malaria transmission
title_full Characterization of Plasmodium developmental transcriptomes in Anopheles gambiae midgut reveals novel regulators of malaria transmission
title_fullStr Characterization of Plasmodium developmental transcriptomes in Anopheles gambiae midgut reveals novel regulators of malaria transmission
title_full_unstemmed Characterization of Plasmodium developmental transcriptomes in Anopheles gambiae midgut reveals novel regulators of malaria transmission
title_short Characterization of Plasmodium developmental transcriptomes in Anopheles gambiae midgut reveals novel regulators of malaria transmission
title_sort characterization of plasmodium developmental transcriptomes in anopheles gambiae midgut reveals novel regulators of malaria transmission
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371638/
https://www.ncbi.nlm.nih.gov/pubmed/25225164
http://dx.doi.org/10.1111/cmi.12363
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