Antimicrobial Properties and Cytotoxicity of LL-37-Derived Synthetic Peptides to Treat Orthopedic Infections.
Pennone. Vincenzo V; Angelini. Elisa E; Sarlah. David D; Lovati. Arianna B AB
Key Findings
- FK‑16 and GF‑17 showed strong antibacterial activity against S. epidermidis and S. aureus (MIC 2‑19 µg/mL)
- Both peptides were non‑toxic to NIH‑3T3 fibroblasts below 75‑150 µg/mL and caused <1% hemolysis at effective doses
- They effectively disrupted bacterial biofilms but showed no synergy with standard antibiotics and no resistance development
Practical Outcomes
- These peptides could become new topical agents or be built into dressings or bone cements to prevent orthopedic infections, but they aren’t yet ready for personal use and need animal studies first.
Summary
Researchers made two short versions of the human antimicrobial peptide LL‑37, called FK‑16 and GF‑17, and tested them in the lab. Both killed common infection‑causing bacteria like Staph epidermidis and Staph aureus at low concentrations, didn’t hurt mouse fibroblast cells or red blood cells at the doses tested, and could break down bacterial biofilms, but they didn’t work better when combined with regular antibiotics and didn’t show any resistance development. The study suggests they might be useful in wound‑care materials, though more animal testing is needed.
Abstract
Open fractures and prosthetic joints are prone to bacterial infections, especially those involving biofilms, and are worsened by antibiotic inefficacy and resistance. This highlights the need for targeted treatments against orthopedic infections. LL-37, a human cathelicidin, is known for its antimicrobial properties. This study aimed to synthesize and evaluate LL-37-derived antimicrobial peptides (AMPs) for antibacterial efficacy and toxicity. Several truncated LL-37 analogues were created and tested against 18 bacterial strains, both ATCC and orthopedic clinical isolates, using MIC and MBC assays. Synergy with antibiotics and resistance development were also analyzed, alongside cytotoxicity on NIH-3T3 fibroblasts and hemolytic activity assessments. Six AMPs were synthesized, with FK-16 and GF-17 emerging as the most effective. The MIC values ranged from 4.69 to 18.75 µg/mL and 2.34 to 18.75 µg/mL, respectively, against <i>S. epidermidis</i> and <i>S. aureus</i>, with the MBC values matching the MIC values. Cytotoxicity tests showed no toxicity at concentrations below 75 µg/mL for GF-17 and 150 µg/mL for FK-16. Hemolytic activity was below 1% at 18.75 µg/mL for GF-17 and 75 µg/mL for FK-16. These AMPs showed no synergistic effects with antibiotics and no resistance development. FK-16 and GF-17 effectively removed biofilms, particularly against <i>S. epidermidis</i>. Incorporating these AMPs into surgical materials (hydrogels, cements, etc.) could enhance infection control in orthopedic procedures, warranting further in vivo studies.
Study Information
pubmed
2024
2024-08-14T00:00:00.000Z
10.3390/antibiotics13080764
6
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