Malaria is one of the three major infectious diseases (AIDS, tuberculosis and malaria) that endanger human health, and the causative agent of malaria is Plasmodium. The most serious harm to humans is Plasmodium falciparum. Gwadz et al. mixed cecropins and magainins on Anopheles infected with Plasmodium, and found that there were no sporozoites in Anopheles, affecting Plasmodium Transmission between Anopheles mosquitoes and humans. This is because antimicrobial peptides interrupt the normal development of oocysts in Anopheles mosquitoes and interfere with the sporogenetic stage of Plasmodium, resulting in the inability to form sporozoites. If the genes encoding cecropins and magainins can be introduced and expressed in the Anopheles mosquito genome, it may induce transmission blocking immunity or produce similar antiparasitic peptide effects, which needs further research to verify. Since antimicrobial peptides were first discovered in the venom of spiders and scorpions in 1990, studies have confirmed that these antimicrobial peptides are biologically active against bacteria, fungi, viruses, and parasites, but have some toxicity to host cells, insects, and red blood cells.

Antiprotozoal mechanism of action of antimicrobial peptides

According to its own unique characteristics, such as amino acid composition, charge, structure, amphiphilicity, hydrophobicity, etc., antimicrobial peptides can easily interact with negatively charged microbial membranes or other cellular targets, destroy the cell membrane structure, and kill directly and quickly. pathogen. Although there is no theory covering all the mechanisms of action of antimicrobial peptides, it is generally accepted that they are mainly membrane action mechanisms and intracellular action mechanisms. Regardless of the mechanism, the two important characteristics of antimicrobial peptides are cationic and amphipathic, which lay the foundation for the innate immune system to recognize pathogen-associated molecular patterns (PAMPs) and exert bactericidal effects.

1. Membrane mechanism of action

The cell membranes of bacteria, fungi and eukaryotes are the primary targets of most antimicrobial peptides, and protozoa are unicellular eukaryotes. Positively charged antimicrobial peptides selectively adsorb and interact with negatively charged cytoplasmic membrane surfaces, changing the permeability of the membrane and forming transmembrane pores on the membrane, preventing cells from maintaining normal osmotic pressure. Substance leakage, leading to disintegration and death of target cells

2. Intracellular mechanism of action

In addition to acting on the cell membrane, antimicrobial peptides can also cause cell apoptosis and death of parasites by affecting the function of intracellular organelles and material transport, and causing nucleic acid degradation. Inner organelle changes and nucleic acid degradation and other forms of antiprotozoal

Today, when antibiotics are abused to produce drug-resistant strains, drug residues and environmental pollution, antimicrobial peptides(custom peptide synthesis) have brought hope to the development of aquaculture and animal husbandry because of their broad spectrum and resistance to drug resistance. However, there are still many challenges to realize the commercial application of antimicrobial peptides. The first is the source of antimicrobial peptides, because the natural peptides extracted from organisms are low in content, difficult to separate and purify, and the cost of chemical synthesis is high. Although the production of antimicrobial peptides using the expression system of genetic engineering technology can be used as a cost-effective model, there are The antibacterial activity of the antibacterial peptide itself has the problem of toxicity to the host cell and the problem of the antibacterial peptide being degraded in the host cell; secondly, the non-natural antibacterial peptide generally has low activity and is easily degraded in the body and cannot maintain an effective concentration for a long time. ; Finally, the hemolysis and drug resistance produced by antimicrobial peptides are also issues that cannot be ignored.

With the continuous deepening of antimicrobial peptide research and the development of biotechnology, the technical barriers for antimicrobial peptides to become drugs for the prevention and treatment of animal protozoa may be broken. First of all, by constructing a suitable expression system, a large number of recombinant antimicrobial peptides with low cost, high yield and high activity can be obtained by fusion expression and tandem expression. Maximize the biological activity of antimicrobial peptides and finally explore the pharmacokinetics of antimicrobial peptides to explore the mechanism of antimicrobial peptides acting in vivo. At present, most of the research on antimicrobial peptides focuses on the modification and optimization of antimicrobial peptides against bacteria and fungi, and there are few data on antiprotozoa. Therefore, in the process of transformation and optimization of antiprotozoal antimicrobial peptides, according to the research purpose, the method of antibacterial antimicrobial peptides was selectively referred to to improve the antiprotozoal activity and expression of antimicrobial peptides, so as to develop efficient and safe antiprotozoal antimicrobial peptides. Formulations provide an important foundation.