Antibacterial Potential of a Novel Peptide from the Consensus Sequence of Dermaseptin Related Peptides Secreted by Agalychnis annae

Curr Pharm Biotechnol. 2021;22(9):1216-1227. doi: 10.2174/1389201021666201020161428.

Abstract

Background: The consistently increasing reports of bacterial resistance and the reemergence of bacterial epidemics have inspired the health and scientific community to discover new molecules with antibacterial potential continuously. Frog-skin secretions constitute bioactive compounds essential for finding new biopharmaceuticals. The exact antibacterial characterization of dermaseptin related peptides derived from Agalychnis annae, is limited. The resemblance in their conserved and functionally linked genomes indicates an unprecedented opportunity to obtain novel bioactive compounds.

Objective: In this study, we derived a novel peptide sequence and determined its antibacterial potentials.

Methods: Consensus sequence strategy was used to design the novel and active antibacterial peptide named 'AGAAN' from skin secretions of Agalychnis annae. The in-vitro activities of the novel peptide against some bacterial strains were investigated. Time kill studies, DNA retardation, cytotoxicity, betagalactosidase, and molecular computational studies were conducted.

Results: AGAAN inhibited P. aeruginosa, E. faecalis, and S. typhimurium at 20 μM concentration. E. coli and S. aureus were inhibited at 25 μM, and lastly, B. subtilis at 50 μM. Kinetics of inactivation against exponential and stationary growing bacteria was found to be rapid within 1-5 hours of peptide exposure, depending on time and concentration. The peptide displayed weak hemolytic activity between 0.01%-7.31% at the antibacterial concentrations. AGAAN efficiently induced bacterial membrane damage with subsequent cell lysis. The peptide's DNA binding shows that it also targets intracellular DNA by retarding its movement. Our in-silico molecular docking analysis displayed a strong affinity to the bacterial cytoplasmic membrane.

Conclusion: AGAAN exhibits potential antibacterial properties that could be used to combat bacterial resistance.

Keywords: Agalychnis annae; Antibacterial peptide; Frogskin secretions; bacterial resistance; consensus sequence; dermaseptin related peptides.

MeSH terms

  • Amino Acid Sequence
  • Amphibian Proteins / chemistry*
  • Animals
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Antimicrobial Cationic Peptides / chemistry*
  • Anura / metabolism*
  • Consensus Sequence
  • DNA / chemistry
  • DNA / metabolism
  • Escherichia coli / drug effects
  • Hemolysis / drug effects
  • Lipid Bilayers / chemistry
  • Lipid Bilayers / metabolism
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Peptides / chemistry*
  • Peptides / metabolism
  • Peptides / pharmacology
  • Protein Conformation, alpha-Helical
  • Pseudomonas aeruginosa / drug effects
  • Sequence Alignment
  • Staphylococcus aureus / drug effects

Substances

  • Amphibian Proteins
  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Lipid Bilayers
  • Peptides
  • dermaseptin
  • DNA