Literature DB >> 25346857

Does Plasmodium falciparum have an Achilles' heel?

Liao Y Chen1.   

Abstract

BACKGROUND: Plasmodium falciparum is the parasite that causes the most severe form of malaria responsible for nearly a million deaths a year. Currently, science has been established about its cellular structures, its metabolic processes, and even the molecular structures of its intrinsic membrane proteins responsible for transporting water, nutrient, and waste molecules across the parasite plasma membrane (PPM). PRESENTATION OF THE HYPOTHESIS: I hypothesize that Plasmodium falciparum has an Achilles' heel that can be attacked with erythritol, the well-known sweetener that is classified as generally safe. This hypothesis is based on the molecular structure of the parasite's membrane and the quantitative mechanics of how erythritol interacts with the multi-functional channel protein expressed in the PPM. Most organisms have in their cell membrane two types of water-channel proteins: aquaporins to maintain hydro-homeostasis across the membrane and aquaglyceroporins to uptake glycerols etc. In contrast, P. falciparum has only one type of such proteins---the multi-functional aquaglyceroporin (PfAQP) expressed in the PPM---to do both jobs. Moreover, the parasite also uses PfAQP to excrete its metabolic wastes (ammonia included) produced at a very high rate in the blood stage. This extremely high efficiency of the bug using one protein for multiple essential tasks makes the parasite fatally vulnerable. Erythritol in the blood stream can kill the parasite by clogging up its PfAQP channel that needs to be open for maintaining hydro-homeostasis and for excreting toxic wastes across the bug's PPM. TESTING THE HYPOTHESIS: In vitro tests are to measure the growth/death rate of P. falciparum in blood with various erythritol concentrations. In vivo experiments are to administer groups of infected mice with various doses of erythritol and monitor the parasite growth levels from blood samples drawn from each group. Clinic trials can be performed to observe the added effects of administering to patients erythritol along with the known drugs because erythritol was classified as a safe food ingredient. IMPLICATIONS OF THE HYPOTHESIS: If proven true, erythritol will cure the most severe form of malaria without significant side effects.

Entities:  

Keywords:  Channel protein; Erythritol; Malaria; P. falciparum

Year:  2014        PMID: 25346857      PMCID: PMC4205581          DOI: 10.4172/2090-2778.1000114

Source DB:  PubMed          Journal:  Malar Chemother Control Elimin        ISSN: 2090-2778


  27 in total

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9.  Aquaporin 9 is the major pathway for glycerol uptake by mouse erythrocytes, with implications for malarial virulence.

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  2 in total

1.  Aquaglyceroporin PbAQP is required for efficient progression through the liver stage of Plasmodium infection.

Authors:  Dominique Promeneur; Godfree Mlambo; Peter Agre; Isabelle Coppens
Journal:  Sci Rep       Date:  2018-01-12       Impact factor: 4.379

2.  Plasmodium parasite exploits host aquaporin-3 during liver stage malaria infection.

Authors:  Dora Posfai; Kayla Sylvester; Anupama Reddy; Jack G Ganley; Johannes Wirth; Quinlan E Cullen; Tushar Dave; Nobutaka Kato; Sandeep S Dave; Emily R Derbyshire
Journal:  PLoS Pathog       Date:  2018-05-18       Impact factor: 6.823

  2 in total

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