Activity of Anti-Microbial Peptides (AMPs) against Leishmania and Other Parasites: An Overview

Abstract

Anti-microbial peptides (AMPs), small biologically active molecules, produced by different organisms through their innate immune system, have become a considerable subject of interest in the request of novel therapeutics. Most of these peptides are cationic-amphipathic, exhibiting two main mechanisms of action, direct lysis and by modulating the immunity. The most commonly reported activity of AMPs is their anti-bacterial effects, although other effects, such as anti-fungal, anti-viral, and anti-parasitic, as well as anti-tumor mechanisms of action have also been described. Their anti-parasitic effect against leishmaniasis has been studied. Leishmaniasis is a neglected tropical disease. Currently among parasitic diseases, it is the second most threating illness after malaria. Clinical treatments, mainly antimonial derivatives, are related to drug resistance and some undesirable effects. Therefore, the development of new therapeutic agents has become a priority, and AMPs constitute a promising alternative. In this work, we describe the principal families of AMPs (melittin, cecropin, cathelicidin, defensin, magainin, temporin, dermaseptin, eumenitin, and histatin) exhibiting a potential anti-leishmanial activity, as well as their effectiveness against other microorganisms.

Keywords: Cathelicidin; Cecropin; Defensin; Dermaseptin; Eumentin; Histatin; Leishmania; Magainin; Melittin; Temporin; anti-bacterial; anti-fungal; anti-microbial peptides (AMPs); anti-parasitic; anti-tumor; anti-viral; bacteria; parasite.

Figure 1

General mechanisms of action of the different families of AMPs with anti-leishmanial activity. Cell membrane disruption is the main mechanism of action adopted by all the described AMPs [50,51,52,53,54,55,56,57,58,59] While some of them present additional mechanisms of action (apoptosis, mitochondrial dysfunction, immune response modulation, and DNA damage) [60,61,62,63,64,65,66]. On the other hand, current drugs used in clinic for leishmaniasis treatment were found to exert similar mechanisms of action. For example, Amphotericin B principally affects the cell membrane [67] and can also modulate the immune response [68]. Miltefosine generates cell death mechanism (apoptosis) [69,70], affects the mitochondrial function [71] and the immune response [72]. Pentavalent antimonials cause DNA damage and can indirectly act by regulating the immune response [73,74].