Most cited article - PubMed ID 31107198
Antimicrobial peptides prevent bacterial biofilm formation on the surface of polymethylmethacrylate bone cement
Microbial resistance is one of the main problems of modern medicine. Recently, antimicrobial peptides have been recognized as a novel approach to overcome the microbial resistance issue, nevertheless, their low stability, toxicity, and potential immunogenic response in biological systems have limited their clinical application. Herein, we present the design, synthesis, and preliminary biological evaluation of polymer-antibacterial peptide constructs. The antimicrobial GKWMKLLKKILK-NH2 oligopeptide (PEP) derived from halictine, honey bee venom, was bound to a polymer carrier via various biodegradable spacers employing the pH-sensitive or enzymatically-driven release and reactivation of the PEP's antimicrobial activity. The antibacterial properties of the polymer-PEP constructs were assessed by a determination of the minimum inhibitory concentrations, followed by fluorescence and transmission electron microscopy. The PEP exerted antibacterial activity against both, gram-positive and negative bacteria, via disruption of the bacterial cell wall mechanism. Importantly, PEP partly retained its antibacterial efficacy against Staphylococcus epidermidis, Escherichia coli, and Acinetobacter baumanii even though it was bound to the polymer carrier. Indeed, to observe antibacterial activity similar to the free PEP, the peptide has to be released from the polymer carrier in response to a pH decrease. Enzymatically-driven release and reactivation of the PEP antimicrobial activity were recognized as less effective when compared to the pH-sensitive release of PEP.
- Keywords
- HPMA copolymers, antimicrobial peptides, bacteria, drug delivery,
- Publication type
- Journal Article MeSH
Polymethylmethacrylate (PMMA) bone cement mixed with antibiotics is used in orthopedic surgery to cope with implant-related infections which are typically associated with the formation of bacterial biofilms. Taking into account the growing bacterial resistance to current antibiotics, we examined here the efficacy of a selected antimicrobial peptide (AMP) mixed into the bone cement to inhibit bacterial adhesion and the consequent biofilm formation on its surface. In particular, we followed the formation of bacterial biofilms of methicillin-resistant Staphylococcus aureus (MRSA) on implants made from PMMA bone cement loaded with AMP composed of 12 amino acid residues. This was evaluated by CFU counting of bacteria released by sonication from the biofilms formed on their surfaces after these implants were retrieved from the infected murine femoral canals. The AMP loaded in these model implants prevented adhesion of MRSA and the subsequent formation of MRSA biofilm on the surfaces of more than 80% of these implants, whereas biofilms did form on control implants made from the plain cement. The results of our experiments performed in the murine femoral canal indicate the potential for this murine osteomyelitis model to mimic actual operations in orthopedics.
- Keywords
- Antimicrobial peptide, Bacterial biofilm, Implant-related infections, Murine model, PMMA implants, Polymethylmethacrylate bone cement,
- MeSH
- Amino Acids MeSH
- Anti-Bacterial Agents pharmacology therapeutic use MeSH
- Antimicrobial Peptides MeSH
- Biofilms MeSH
- Bone Cements MeSH
- Methicillin-Resistant Staphylococcus aureus * MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Orthopedic Procedures * MeSH
- Polymethyl Methacrylate chemistry MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Amino Acids MeSH
- Anti-Bacterial Agents MeSH
- Antimicrobial Peptides MeSH
- Bone Cements MeSH
- Polymethyl Methacrylate MeSH
A projected increased use of total joint arthroplasties will naturally result in a related increase in the number of prosthetic joint infections (PJIs). Suppression of the local peri-implant immune response counters efforts to eradicate bacteria, allowing the formation of biofilms and compromising preventive measures taken in the operating room. For these reasons, the prevention of PJI should focus concurrently on the following targets: (i) identifying at-risk patients; (ii) reducing "bacterial load" perioperatively; (iii) creating an antibacterial/antibiofilm environment at the site of surgery; and (iv) stimulating the local immune response. Despite considerable recent progress made in experimental and clinical research, a large discrepancy persists between proposed and clinically implemented preventative strategies. The ultimate anti-infective strategy lies in an optimal combination of all preventative approaches into a single "clinical pack", applied rigorously in all settings involving prosthetic joint implantation. In addition, "anti-infective" implants might be a choice in patients who have an increased risk for PJI. However, further progress in the prevention of PJI is not imaginable without a close commitment to using quality improvement tools in combination with continual data mining, reflecting the efficacy of the preventative strategy in a particular clinical setting.
