Does Plasmodium falciparum have an Achilles' heel?

Liao Y Chen

doi:10.4172/2090-2778.1000114

Abstract

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). 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. 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. If proven true, erythritol will cure the most severe form of malaria without significant side effects.

Highlights

Does Plasmodium falciparum the parasite that causes the most severe form of malaria leading to the death of a child every 60 second [1] have an Achilles’ heel that can be exploited therapeutically? The answer seems to be yes even though the bug enjoys three layers of protection by the red cell membrane (RCM), the parasitorphorous vacuole membrane (PVM), and the parasite plasma membrane (PPM)
On the basis of the molecular structure of the bug’s PPM and the quantitative mechanics of its major intrinsic membrane protein interacting with erythritol, I hypothesize that erythritol [2] the generally considered safe sugar substitute [3] could be the weapon needed to deliver a fatal attack on the heel of the parasite that is responsible for about a million deaths a year
Researchers have not considered the possibility that the benign erythritol can kill or impede the growth of P. falciparum

Summary

Introduction

Does Plasmodium falciparum the parasite that causes the most severe form of malaria leading to the death of a child every 60 second [1] have an Achilles’ heel that can be exploited therapeutically? The answer seems to be yes even though the bug enjoys three layers of protection by the red cell membrane (RCM), the parasitorphorous vacuole membrane (PVM), and the parasite plasma membrane (PPM). In vitro tests are to measure the growth/death rate of P. falciparum in blood with various erythritol concentrations. AQP---Aquaporin/Aquaglyceroporin PfAQP---Plasmodium falciparum aquaglyceroporin PPM---Parasite plasma membrane PVM---Parasitorphorous vacuole membrane RCM---Red cell membrane

Results

Conclusion