Antimicrobial activity of synthetic Dq-3162, a 28-residue ponericin G-like dinoponeratoxin from the giant ant Dinoponera quadriceps venom, against carbapenem-resistant bacteria

Toxicon. 2020 Nov:187:19-28. doi: 10.1016/j.toxicon.2020.08.015. Epub 2020 Aug 27.

Abstract

The predatory giant ant Dinoponera quadriceps is one of the largest venomous ants on Earth. The venom of D. quadriceps comprises a rich blend of bioactive peptides that includes structures related to at least five classes of antimicrobial peptides. In the present study, two representative synthetic peptides, sDq-2562 and sDq-3162, belonging to the ponericin-like dinoponeratoxin family, were evaluated for their microbicide activity against antibiotic-resistant bacteria. The most effective peptide, the 28-residue sDq-3162 displayed a significant bacteriostatic and bactericidal effect with minimal inhibitory concentrations (MICs) between 5 μM and 10 μM (15.6 μg mL-1 and 31.2 μg mL-1), according to the strain of drug-resistant bacteria tested. In combination with conventional antibiotics, sDq-3162 displayed in vitro synergistic effects, reducing the MICs of antibiotics for more than 2-log against clinical isolates of carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa, with low cytotoxicity to human erythrocytes, in vitro. Since the development of molecules to circumvent the spread of antibiotic-resistant bacteria is demanding, ant venom peptides arise as useful molecular resources to contribute with the antimicrobial arsenal and therapeutic strategies to fight clinically relevant microbial infections.

Keywords: Ant venom peptide; Anti-infective agent; Antibiotic-resistant bacteria; Antimicrobial peptide; Dinoponera quadriceps; Dinoponeratoxin.

MeSH terms

  • Animals
  • Ant Venoms / toxicity*
  • Anti-Infective Agents / toxicity*
  • Ants
  • Bacteria
  • Carbapenems
  • Microbial Sensitivity Tests
  • Peptides
  • Pseudomonas aeruginosa / drug effects

Substances

  • Ant Venoms
  • Anti-Infective Agents
  • Carbapenems
  • Peptides