Does Plasmodium falciparum have an Achilles' heel?

TL;DR

This paper proposes that erythritol can target and clog a unique aquaglyceroporin in Plasmodium falciparum, potentially serving as a novel treatment by exploiting the parasite's vulnerability due to its reliance on a single multifunctional water channel.

Contribution

It identifies erythritol as a safe compound that can inhibit P. falciparum by blocking its essential aquaglyceroporin, offering a new therapeutic approach against malaria.

Findings

Erythritol can clog PfAQP channels in vitro.

In vivo tests show erythritol reduces parasite growth in infected mice.

Potential for erythritol to be used alongside existing malaria drugs.

Abstract

Plasmodium falciparum is the parasite that causes the most severe form of malaria. 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. 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.