Evaluation of original, and bioinformatically modifiable, marine antimicrobial peptides as trypanocidal agents.

• Grant number: 23/08572-5
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• Start date: April 30, 2024
• End date: July 27, 2024
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Ariel Mariano Silber
• Grantee: Ariel Mariano Silber
• Visiting researcher: Anselmo de Jesus Otero-Gonzalez
• Visiting researcher institution: Universidad de La Habana (UH), Cuba
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/12938-0 - Amino acid metabolism in Trypanosoma cruzi: a toolbox to survive in hostile environments, AP.TEM

Abstract

Chagas disease, also called American trypanosomiasis, is a life-threatening disease caused by the protozoan parasite Trypanosoma cruzi. It is estimated that in the world there are between six and seven million people infected with T. cruzi. The disease is endemic in the Americas, where it is transmitted to humans and other mammals mainly through the feces or urine of triatomines (vectorial route). Chagas disease can be treated with benznidazole (Bz) or nifurtimox (Nf), which kill the parasite. Both drugs are fully effective in curing the disease if administered early in the infection in the acute stage, including cases of congenital transmission. However, its effectiveness decreases in chronic patients, and adverse reactions are frequent in adults. As most of the patients are diagnosed during the chronic infection, when Bz and Nf are less efficient, new chemotherapeutic compounds are needed to treat this devastating disease1. Invertebrates have been shown to express a wide variety of antimicrobial peptides2. Other sources as marine and fluvial mollusks, could offer therapeutic peptide candidates against membrane or metabolic T.cruzi targets. Some Antimicrobial peptides previously characterized are available to explore their possibilities as trypanocidal agents3,4,5,6. In this ongoing collaboration, the laboratories of Prof. Silber and Prof. Otero from Havana University are intending to evaluate the activity of mollusk antimicrobial peptides and to elucidate their mechanism of action of the original peptide version and the subsequent bioinformatically developed derivatives able to improve in vitro antiparasitic activity. This collaboration is intended to open a new vista in the scope of Prof. Silber´s laboratory and to expand the repertory of these previously published mollusk-derived antimicrobial peptides. (AU)