Synthetic anti‐endotoxin peptides interfere with Gram‐positive and Gram‐negative bacteria, their adhesion and biofilm formation on titanium

Abstract

Aims: Implant-associated infections arise from the formation of bacterial biofilms, which are difficult to be treated with conventional antibiotics. Therefore, there is a need for new implant functionalizations, which inhibit biofilm formation. The aim of the present study was to characterize the effect of synthetic peptides to assess their applicability for this purpose. Methods and Results: Two synthetic anti-endotoxin peptides, Pep19-2.5 and Pep19-4LF (Aspidasept I and II) were tested against both Gram-positive (Staphylococcus aureus and Streptococcus oralis) and Gram-negative (Pseudomonas aeruginosa and Aggregatibacter actinomycetemcomitans) bacteria associated with implant infections. Their activity was evaluated against different states of biofilm formation on the implant material titanium using CFU, live/dead fluorescence staining and confocal microscopy. Both peptides inhibited planktonic bacteria growth, impacted initial bacterial adhesion, reduced biofilm volume and increased the proportion of dead cells. Additionally, cytotoxicity analyses showed that neither peptide harmed human gingival fibroblasts nor osteoblasts at lower concentrations. Conclusion: A concentration-dependent antibacterial activity of both peptides against biofilms of four clinically relevant bacteria could be demonstrated. Significance and Impact of the Study: The results of this study serve as a promising basis for the improvement of these peptides in order to finally achieve a peptide-equipped antibacterial implant surface.

Oriented immobilization of Pep19-2.5 on antifouling brushes suppresses the development of Staphylococcus aureus biofilms

“…The functionalization with Pep19-2.5 afforded a further decrease in biofilm formation, with a biovolume reduction of 24.2% compared to glass. A similar reduction of biofilm biovolume was reported for S. aureus biofilm treated with free Pep19-2.5 (without DBCO) [63]. Moreover, the architecture of the biofilm on MeOEGMA-Pep19-2.5 is drastically different than the ones observed on glass and MeOEGMA-N 3 .…”

“…Importantly, this peptide has a wide spectrum of action associated with high affinity not only to the LPS factor of Gram-negative bacteria but also to lipoprotein (LP) of Gram-positive ones [62]. Moreover, recent pioneering studies had shown that Pep19-2.5 reduced bacterial adhesion and biofilm formation of titanium samples from both Staphylococcus aureus, Streptococcus oralis, Pseudomonas aeruginosa, and Aggregatibacter actinomycetemcomitans [63]. Furthermore, it demonstrates very low cytotoxicity and can reduce the level of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) [64] as well as to attenuate cardiomyopathy in the septic heart [65,66].…”

Adhesion Forces of Oral Bacteria to Titanium and the Correlation with Biophysical Cellular Characteristics

“…Bacterial adhesion was analyzed on titanium, one of the most common implant materials. Roughness of the test specimens was chosen to match established parameters for reliable control surfaces routinely used in antibacterial materials research [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. The surface roughness sometimes caused scattering photons in the AFM laser to interfere with the reflected laser beam, resulting in incomplete approach or sinus-shaped artefacts in the force–distance curves.…”

Recent Progress in Bile Acid-Based Antimicrobials

“…Natural occurring antimicrobial peptides (AMPs), also named host defense peptides, have broad-spectrum antimicrobial activity. Currently, the most approved antimicrobial mechanism is the membrane targeted mechanism, resulting in low probability of drug resistance. − Structurally, the majority of linear AMPs are typically facial amphiphilic that have clear hydrophilic/hydrophobic regions assembled by their secondary structures of α-helix or β-sheet and facilitate interactions with bacterial membranes (Figure a). − AMPs and their analogues are usually synthesized via solid-phase synthesis technology, − but high cost of production, relatively low stability in vivo, and limited bioavailability hinder their applications in clinic. To circumvent these issues, diverse polymeric antimicrobials are prepared such as polymaleimide, polymethacrylates, − polycarbonates, polyionenes, − polyamide via ring-opening polymerization (ROP), ,− and others ,− to mimic AMPs.…”