Trypanosomatid Aquaporins: Roles in Physiology and Drug Response

Goutam Mandal,Mansi Sharma,Rita Mukhopadhyay,Jose Orta

doi:10.3390/diseases2010003

Abstract

In the class Kinetoplastida, we find an order of parasitic protozoans classified as Trypanosomatids. Three major pathogens form part of this order, Trypanosoma cruzi, Trypanosoma brucei, and Leishmania, which are responsible for disease and fatalities in millions of humans worldwide, especially in non-industrialized countries in tropical and sub-tropical regions. In order to develop new drugs and treatments, the physiology of these pathogenic protozoans has been studied in detail, specifically the significance of membrane transporters in host parasites interactions. Aquaporins and Aquaglyceroporins (AQPs) are a part of the major intrinsic proteins (MIPs) super-family. AQPs are characterized for their ability to facilitate the diffusion of water (aquaporin), glycerol (aquaglyceroporin), and other small-uncharged solutes. Furthermore, AQPs have been shown to allow the ubiquitous passage of some metalloids, such as trivalent arsenic and antimony. These trivalent metalloids are the active ingredient of a number of chemotherapeutic agents used against certain cancers and protozoan parasitic infections. Recently, the importance of the AQPs not only in osmotic adaptations but also as a factor in drug resistance of the trypanosomatid parasites has been reported. In this review, we will describe the physiological functions of aquaporins and their effect in drug response across the different trypanosomatids.

Highlights

Trypanosomatid parasites are single celled pathogenic organisms considered a major cause of morbidity and mortality in tropical and subtropical regions worldwide
Caused by L. infantum and L. chagasi can be both zoonotic or anthroponotic whereas only anthroponotic transmission has been reported for visceral leishmaniasis (VL) caused by L. donovani [30]
VL is reported to be caused by L. donovani (Asia and Africa), L. infantum (Europe) and L. chagasi (New World) [30,31,32]

Summary

Introduction

Trypanosomatid parasites are single celled pathogenic organisms considered a major cause of morbidity and mortality in tropical and subtropical regions worldwide. Plasmodium AQPs are permeable to water, glycerol, urea, and several other polyols This AQP is not essential for the parasite survival, glycerol transport through this channel plays a significant role during gametocytes development inside the red blood cells [18]. The levels of sensitivity against these compounds are far from ideal for clinical studies, these show promise that cytotoxic AQP substrates can be used for treating parasitic infections Metalloids, such as arsenic and antimony, permeability of AQPs have been exploited to treat several human diseases for more than a century. AQPs in trypanosomatid parasites with respect to physiology and drug response

Life Cycle

Disease

Treatment and Drug Resistance

Role of AQP in Parasite Physiology and Drug Response

Findings

Conclusions