Natural Occurrence in Venomous Arthropods of Antimicrobial Peptides Active against Protozoan Parasites

Abstract

Arthropoda is a phylum of invertebrates that has undergone remarkable evolutionary radiation, with a wide range of venomous animals. Arthropod venom is a complex mixture of molecules and a source of new compounds, including antimicrobial peptides (AMPs). Most AMPs affect membrane integrity and produce lethal pores in microorganisms, including protozoan pathogens, whereas others act on internal targets or by modulation of the host immune system. Protozoan parasites cause some serious life-threatening diseases among millions of people worldwide, mostly affecting the poorest in developing tropical regions. Humans can be infected with protozoan parasites belonging to the genera Trypanosoma, Leishmania, Plasmodium, and Toxoplasma, responsible for Chagas disease, human African trypanosomiasis, leishmaniasis, malaria, and toxoplasmosis. There is not yet any cure or vaccine for these illnesses, and the current antiprotozoal chemotherapeutic compounds are inefficient and toxic and have been in clinical use for decades, which increases drug resistance. In this review, we will present an overview of AMPs, the diverse modes of action of AMPs on protozoan targets, and the prospection of novel AMPs isolated from venomous arthropods with the potential to become novel clinical agents to treat protozoan-borne diseases.

Keywords: Chagas disease; antimicrobial peptide; arthropod; human African trypanosomiasis; leishmaniasis; malaria; toxoplasmosis; venom.

Figure 1

Mode of action of antiprotozoal AMPs. (left): Direct microbial action and possible membrane/internal targets of AMPs. (right): Modulation caused by AMPs in different types of cells, molecules and processes in mammals’ immune system.

Figure 2

Schematic overview of a protozoan cell with various internal targets (highlighted in red) of AMPs.

Figure 3

Schematic life cycle of T. cruzi. The blue arrows indicate life stages in the definitive host (human). The red arrows indicate life stages in the vector of CD. The green boxes illustrate the AMPs described with activity against each specific developmental form of the parasite.

Figure 4

Schematic life cycle of T. brucei. The blue arrows indicate life stages in the definitive host (human). The red arrows indicate life stages in the vector of human African trypanosomiasis. The green box illustrates the AMP described with activity against the specific developmental form of the parasite.

Figure 5

Schematic life cycle of Leishmania. The blue arrows indicate life stages in the definitive host (human). The red arrows indicate life stages in the vector of leishmaniasis. The green boxes illustrate the AMPs described with activity against each specific developmental form of the parasite.

Figure 6

Schematic life cycle of Plasmodium. The blue arrows indicate life stages in the definitive host (human). The red arrows indicate life stages in the vector of malaria. The green boxes illustrate the AMPs described with activity against each specific developmental form of the parasite.

Figure 7

Schematic life cycle of T. gondii. The blue arrows indicate life stages in the intermediate hosts (exo-enteric cycle). The red arrows indicate life stages in the definitive host of toxoplasmosis (enteric cycle). The green box illustrates the AMPs described with activity against the specific developmental form of the parasite.