OMN6 a novel bioengineered peptide for the treatment of multidrug resistant Gram negative bacteria

Sci Rep. 2021 Mar 23;11(1):6603. doi: 10.1038/s41598-021-86155-9.

Abstract

New antimicrobial agents are urgently needed, especially to eliminate multidrug resistant Gram-negative bacteria that stand for most antibiotic-resistant threats. In the following study, we present superior properties of an engineered antimicrobial peptide, OMN6, a 40-amino acid cyclic peptide based on Cecropin A, that presents high efficacy against Gram-negative bacteria with a bactericidal mechanism of action. The target of OMN6 is assumed to be the bacterial membrane in contrast to small molecule-based agents which bind to a specific enzyme or bacterial site. Moreover, OMN6 mechanism of action is effective on Acinetobacter baumannii laboratory strains and clinical isolates, regardless of the bacteria genotype or resistance-phenotype, thus, is by orders-of-magnitude, less likely for mutation-driven development of resistance, recrudescence, or tolerance. OMN6 displays an increase in stability and a significant decrease in proteolytic degradation with full safety margin on erythrocytes and HEK293T cells. Taken together, these results strongly suggest that OMN6 is an efficient, stable, and non-toxic novel antimicrobial agent with the potential to become a therapy for humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter baumannii / drug effects*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / chemistry
  • Bacterial Outer Membrane / drug effects
  • Drug Resistance, Multiple, Bacterial
  • Pore Forming Cytotoxic Proteins / chemistry
  • Pore Forming Cytotoxic Proteins / pharmacology*
  • Protein Engineering
  • Protein Stability

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Pore Forming Cytotoxic Proteins
  • cecropin A