Efeito de análogos da dinoponeratoxina M-PONTX-Dq3a sobre cepas de bactérias gram-negativas

Abstract

Antimicrobial resistance is a health problem in Brazil and around the world, gram-negative bacteria stand out at this point, considering that they are microorganisms normally found in hospital infections (54.8%), accompanied by gram-positive bacteria (23.8%). %) and yeasts (21.4%). In this context, it is known that the venoms of venomous animals are important sources of antimicrobial peptides. The ant Dinoponera quadriceps is one of the largest poisonous ants on earth, its venom is a rich mixture of antimicrobial peptides. In the present study, the antimicrobial activity of M-PONTX-Dq3a and eight synthetic analogues substituted by arginine and lysine in strategic positions in the molecule was investigated against gram-negative bacteria, namely Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosas. For this, tests were carried out to determine the Minimum Inhibitory Concentration (MIC) through the broth microdilution test, in vitro synergism with commercially available antimicrobials using the checkerboard method, evaluation of the hemolytic potential of the peptides and renal toxicity under renal lineage cells. human HK-2 type. The peptides that showed the greatest antimicrobial effect for the ATCC and clinical strains tested were [Arg]3 M-PONTX-Dq3a[1–15] and [Arg]4 M-PONTX-Dq3a[1–15], reaching MIC and CLM of 1.56 μM for ATCC strain and 0.19 μM for clinical strain. The bacteria that showed the greatest sensitivity to these peptides was E. coli ATCC 25922 and clinical. The peptide [Arg]3 M-PONTX-Dq3a[1–15] presented a bactericidal profile and [Arg]4 M-PONTX-Dq3a[1–15] presented a bactericidal and bacteriostatic profile. A synergistic effect was obtained between ciprofloxacin with [Arg]3 M-PONTX-Dq3a[1–15] and [Arg]4 M-PONTX-Dq3a[1–15] under E. coli ATCC 25922, managing to reduce the concentration by up to 4x of the antibiotic, showing that they are promising peptides for combinations with other antimicrobials that are already used on the market. Thus, as they presented a greater therapeutic effect, the modified peptides [Arg]3 M-PONTX-Dq3a[1–15] and [Arg]4 M-PONTX-Dq3a[1–15] also obtained results demonstrating their cytotoxic effect on erythrocytes and human kidney cells, and there may be benefits from nanotechnology in subsequent studies that can assist in the development of a molecule more directed to the therapeutic target, which has a pronounced antimicrobial effect and reduced side effects.