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  • 标题:Aquaglyceroporin PbAQP is required for efficient progression through the liver stage of Plasmodium infection
  • 本地全文:下载
  • 作者:Dominique Promeneur ; Godfree Mlambo ; Peter Agre
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2018
  • 卷号:8
  • 期号:1
  • 页码:655
  • DOI:10.1038/s41598-017-18987-3
  • 语种:English
  • 出版社:Springer Nature
  • 摘要:The discovery of aquaglyceroporins (AQP) has highlighted a new mechanism of membrane solute transport that may hold therapeutic potential for controlling parasitic infections, including malaria. Plasmodium parasites express a single AQP at the plasma membrane that functions as a channel for water, nutrients and waste into and out cells. We previously demonstrated that Plasmodium berghei targeted for PbAQP deletion are deficient in glycerol import and less virulent than wild-type parasites during the blood developmental stage. Here, we have examined the contribution of PbAQP to the infectivity of P. berghei in the liver. PbAQP is expressed in the sporozoite mosquito stage and is detected at low levels in intrahepatic parasites at the onset of hepatocyte infection. As the parasites progress to late hepatic stages, PbAQP transcription increases and PbAQP localizes to the plasma membrane of hepatic merozoites. Compared to wild-type parasites, PbAQP-null sporozoites exhibit a delay in blood stage infection due to slower replication in hepatocytes, resulting in retardation of merosome production. Furthermore, PbAQP disruption results in a significant reduction in erythrocyte infectivity by hepatocyte-derived merozoites. Hepatic merozoites incorporate exogenous glycerol into glycerophospholipids and PbAQP-null merozoites contain less phosphatidylcholine than wild-type merozoites, underlining the contribution of Plasmodium AQP to phospholipid syntheses.
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