Abstract
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.
Highlights
Malaria is due to protozoan parasites of the genus Plasmodium, and this parasitic infection causes a global health epidemic with considerable morbidity and ∼429,000 deaths in 2015 according to WHO
As a first approach to investigate the importance of PbAQP for the liver stage, we examined the transcriptional profiles of PbAQP during parasite development in liver cells from 24 h to 60 h, which corresponds to the duration of the intrahepatic development of P. berghei
Our previous study reported that the single PbAQP gene expressed by P. berghei contributes in part to parasite development in red blood cells[5]
Summary
Malaria is due to protozoan parasites of the genus Plasmodium, and this parasitic infection causes a global health epidemic with considerable morbidity and ∼429,000 deaths in 2015 according to WHO (www.who.int/gho/ malaria). A single multifunctional aquaglyceroporin channeling selective substrates is expressed by P. falciparum (PfAQP) and by the rodent parasite Plasmodium berghei (PbAQP) at the plasma membrane where it mediates the passage of glycerol, water, urea, small polyols and carbonyl compounds through its amphipathic pore[4,5,6]. Malaria parasites as they face drastic osmotic changes during host tissue migration Due to their rapid growth, Plasmodium sp. The function and localization of Plasmodium AQP as well as its contribution to parasite development have been only investigated for the malaria asexual blood stage. Using the P. berghei rodent malaria model, we showed that PbAQP is predominantly expressed during late stage development in hepatocytes. By exploiting PbAQP-null parasites[5], we determined that PbAQP is required for efficient progression through the liver stage of infection and phospholipid synthesis in hepatic merozoites
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