Bioactivity of synthetic peptides from Ecuadorian frog skin secretions against
Leishmania mexicana
,
Plasmodium falciparum
, and
Trypanosoma cruzi
Authors: Proaño-Bolaños Carolina , Morán-Marcillo Giovanna , Espinosa de los Monteros-Silva Nina , Bermúdez-Puga Sebastián , Salazar Mateo A. , Blasco-Zúñiga Ailín , Cuesta Sebastián , Molina Carolina , Espinosa Franklin , Meneses Lorena , Rojas-Silva Patricio , Zapata Mena Sonia , Sáenz Fabián E. , Rivera I. Miryan , Costales Jaime A. 
Published: July 2024

Chagas disease, leishmaniasis, and malaria are major parasitic diseases disproportionately affecting the underprivileged population in developing nations. Finding new, alternative anti-parasitic compounds to treat these diseases is crucial because of the limited number of options currently available, the side effects they cause, the need for long treatment courses, and the emergence of drug-resistant parasites. Anti-microbial peptides (AMPs) derived from amphibian skin secretions are small bioactive molecules capable of lysing the cell membrane of pathogens while having low toxicity against human cells. Here, we report the anti-parasitic activity of five AMPs derived from skin secretions of three Ecuadorian frogs: cruzioseptin-1, cruzioseptin-4 (CZS-4), and cruzioseptin-16 from
Cruziohyla calcarifer
; dermaseptin-SP2 from
Agalychnis spurrelli
; and pictuseptin-1 from
Boana picturata
. These five AMPs were chemically synthesized. Initially, the hemolytic activity of CZS-4 and its minimal inhibitory concentration against
Escherichia coli
,
Staphylococcus aureus
, and
Candida albicans
were determined. Subsequently, the cytotoxicity of the synthetic AMPs against mammalian cells and their anti-parasitic activity against
Leishmania mexicana
promastigotes, erythrocytic stages of
Plasmodium falciparum
and mammalian stages of
Trypanosoma cruzi
were evaluated
in vitro
. The five AMPs displayed activity against the pathogens studied, with different levels of cytotoxicity against mammalian cells.
In silico
molecular docking analysis suggests this bioactivity may occur via pore formation in the plasma membrane, resulting in microbial lysis. CZS-4 displayed anti-bacterial, anti-fungal, and anti-parasitic activities with low cytotoxicity against mammalian cells. Further studies about this promising AMP are required to gain a better understanding of its activity.

IMPORTANCE

Chagas disease, malaria, and leishmaniasis are major tropical diseases that cause extensive morbidity and mortality, for which available treatment options are unsatisfactory because of limited efficacy and side effects. Frog skin secretions contain molecules with anti-microbial properties known as anti-microbial peptides. We synthesized five peptides derived from the skin secretions of different species of tropical frogs and tested them against cultures of the causative agents of these three diseases, parasites known as
Trypanosoma cruzi
,
Plasmodium falciparum
, and
Leishmania mexicana
. All the different synthetic peptides studied showed activity against one of more of the parasites. Peptide cruzioseptin-4 is of special interest since it displayed intense activity against parasites while being innocuous against cultured mammalian cells, which indicates it does not simply hold general toxic properties; rather, its activity is specific against the parasites.