Antibacterial Activity on Orthopedic Clinical Isolates and Cytotoxicity of the Antimicrobial Peptide Dadapin-1

Int J Mol Sci. 2023 Jan 2;24(1):779. doi: 10.3390/ijms24010779.

Abstract

In orthopedic surgery, biomaterial-associated infections represent a complication of serious concern. Most promising strategies to prevent these infections currently rely on the use of anti-infective biomaterials. Desirably, in anti-infective biomaterials, the antibacterial properties should be achieved by doping, grafting, or coating the material surfaces with molecules that are alternative to conventional antibiotics and exhibit a potent and highly specific activity against bacteria, without altering the biocompatibility. Antimicrobial peptides (AMPs) are among the most interesting candidate molecules for this biomaterial functionalization. Here, the potential expressed by the recently discovered peptide Dadapin-1 was explored by assaying its MIC, MBIC and MBC on clinical strains of relevant bacterial species isolated from orthopedic infections and by assessing its cytotoxicity on the human osteoblast-like MG63 cells. When appropriately tested in diluted Mueller Hinton Broth II (MHB II), Dadapin-1 exhibited significant antibacterial properties. MIC values were in the range of 3.1-6.2 µM for the gram-positive bacteria Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus warneri, and 12.4-24.9 µM for the gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa. Interestingly, the peptide was found non-cytotoxic, with an IC50 exceeding the highest concentration tested of 179 µM. Overall, Dadapin-1 expresses considerable potential for future application in the production of anti-infective biomaterials.

Keywords: Dadapin-1; anti-infective biomaterials; antimicrobial peptides; cytotoxicity; implant infections; orthopaedic infections.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents* / chemistry
  • Antimicrobial Peptides*
  • Biocompatible Materials
  • Escherichia coli
  • Humans
  • Microbial Sensitivity Tests
  • Peptides / chemistry
  • Peptides / pharmacology
  • Staphylococcus epidermidis

Substances

  • Antimicrobial Peptides
  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Peptides
  • Biocompatible Materials

Grants and funding

The financial contribution by the Theory-enhancing Project RF-2018-12368273: “Implant orthopaedic infections: the challenge of bacterial antibiotic resistance and new anti-infective materials” funded by the Ministry of Health for the IRCCS Rizzoli Orthopedic Institute of Bologna is gratefully acknowledged.