The dinoponeratoxin peptides from the giant ant Dinoponera quadriceps display in vitro antitrypanosomal activity

Abstract

The crude venom of the giant ant Dinoponera quadriceps is a cocktail of polypeptides and organic compounds that shows antiparasitic effects against Trypanosoma cruzi, the causative agent of Chagas disease. In order to investigate the venom-derived components responsible for such antitrypanosomal activity, four dinoponeratoxins (DnTxs) were identified, namely M-PONTX-Dq3a, -Dq3b, -Dq3c and -Dq4e, that are diverse in size, net charge, hydrophobicity and propensity to interact with eukaryote cell membranes. These peptides were tested against epimastigote, trypomastigote and amastigote forms of benznidazole (Bz)-resistant Y strain of T. cruzi and in mammalian host cells. The M-PONTX-Dq3a and -Dq4e inhibited all developmental forms of T. cruzi, including amastigotes, the responsible form for the maintenance of infection on chronic phase of the disease. The M-PONTX-Dq3a showed the highest selectivity index (SI) (80) and caused morphological alterations in T. cruzi, as observed by scanning electron microscopy (SEM), and induced cell death through necrosis, as seen by multiparametric flow cytometry analysis with specific biochemical markers. Altogether, the D. quadriceps venom appears as a source for the prospection of trypanocidal peptides and the M-PONTX-Dq3a arises as a candidate among the dinoponeratoxin-related peptides in the development of compounds against Chagas disease.

It Takes Two: Dimerization Is Essential for the Broad-Spectrum Predatory and Defensive Activities of the Venom Peptide Mp1a from the Jack Jumper Ant Myrmecia pilosula

“…Mp1a and synthetic analogues have already been shown to have antibiotic activity, including against the opportunistic human pathogen Acinetobacter baumannii [ 5 ]. Several venom-derived antimicrobial peptides are active against a range of human parasites, including cupiennin 1a from the wandering spider Cupiennius salei , which is active against both trypanosomes and malaria parasites [ 15 , 16 ], the antimalarial peptides meucin-24 and 25 from the scorpion Mesobuthus eupeus [ 17 ], and the antitrypanosomal dinoponeratoxins from the giant ant Dinoponera quadriceps [ 18 ]. We therefore explored whether Mp1a might be active against Haemonchus contortus , a pathogenic blood-feeding parasitic nematode of ruminants, which serves as a model organism for anthelmintic drug discovery.…”

Venom alkaloids against Chagas disease parasite: search for effective therapies

“…Among venomous insects, ants are remarkably chemically diverse 42 , as illustrated by a recent increase in the number of studies surveying the biomedical applications of ant toxins, such as the Brazilian giant ant Dinoponera quadriceps 43 . Among several other biomedical activities, the venom peptides of D. quadriceps were reported to be toxic to T. cruzi 44 . Notwithstanding, the venom alkaloids of ants have remained untested against trypanosomatids.…”

Antichagasic effect of violacein from Chromobacterium violaceum

“…The trypomastigote forms of T. cruzi obtained by infecting LLCMK2 cells were incubated at 37°C in an atmosphere with 5% CO 2 in DMEM medium (Vitrocell, São Paulo, Brazil) supplemented with antibiotics and 2% of FBS (Lima et al . ). Intracellular amastigotes were obtained and cultured as described in section 2·6.…”

“…The epimastigote forms were treated with EC 50 (51·39 μmol l −1 ) and 2 × EC 50 (102·78 μmol l −1 ) of VIO for 24 h. After incubation, the parasites were fixed for 2 h with 2·5% glutaraldehyde (Electron Microscopy Sciences, Hatfield, PA) washed, dehydrated, dried with CO 2 , coated in gold and observed in a FEG Quanta 450 scanning electron microscope (SEM) (FEI, OR). Digital images were acquired and stored in a computer (Lima et al ).…”