An Antibacterial Peptide with High Resistance to Trypsin Obtained by Substituting d-Amino Acids for Trypsin Cleavage Sites

The poor stability of antibacterial peptide to protease limits its clinical application. Among these limitations, trypsin mainly exists in digestive tract, which is an insurmountable obstacle to orally delivered peptides. OM19R is a random curly polyproline cationic antimicrobial peptide, which has high antibacterial activity against some gram-negative bacteria, but its stability against pancreatin is poor. According to the structure-activity relationship of OM19R, all cationic amino acid residues (l-arginine and l-lysine) at the trypsin cleavage sites were replaced with corresponding d-amino acid residues to obtain the designed peptide OM19D, which not only maintained its antibacterial activity but also enhanced the stability of trypsin. Proceeding high concentrations of trypsin and long-time (such as 10 mg/mL, 8 h) treatment, it still had high antibacterial activity (MIC = 16–32 µg/mL). In addition, OM19D also showed high stability to serum, plasma and other environmental factors. It is similar to its parent peptide in secondary structure and mechanism of action. Therefore, this strategy is beneficial to improve the protease stability of antibacterial peptides.

Antibacterial Peptide HHC-36 Sustained-Release Coating Promotes Antibacterial Property of Percutaneous Implant

Percutaneous implants are widely used in clinical practice. However, infection is the main clinical problem of percutaneous implants. Titanium dioxide nanotubes are suitable for forming coatings on complex surfaces such as implants. HHC-36, a cationic antimicrobial peptide, has been identified to have a strong broad-spectrum antibacterial effect. In the present study, we use poly D,L-lactic acid (PDLLA) and poly lactic-co-glycolic acid (PLGA) coating to build HHC-36 sustained-release system on the surface of titanium dioxide nanotubes. The titanium specimens were anodized coated with HHC-36-PDLLA/PLGA. The morphology and surface elemental distribution of the specimens were evaluated. Besides, results in the present study demonstrated that with antibacterial peptide HHC-36 sustained-release coating, titanium dioxide nanotubes maintain effective drug release for 15 days in vitro, and show significant antibacterial activity. The proliferation of Staphylococcus aureus can be effectively inhibited by PDLLA/PLGA-HHC-36 coated titanium dioxide nanotube. In addition, PDLLA-HHC-36 and PLGA-HHC-36 coating was demonstrated to be biocompatible and antibacterial in vivo. These findings demonstrated that HHC-36 coated titanium nanotube could improve antibacterial potential of percutaneous implants, and indicated a novel and efficient strategy in preventing bacterial infection of percutaneous implants.

Bacteroidetocins Target the Essential Outer Membrane Protein BamA of Bacteroidales Symbionts and Pathogens

The bacteroidetocins are a newly discovered class of bacteriocins specific to Bacteroidetes with a spectrum of targets extending from symbiotic gut Bacteroides , Parabacteroides , and Prevotella species to pathogenic oral and vaginal Prevotella species. We previously showed that one such bacteroidetocin, Bd-A, is active at nanomolar concentrations, is water soluble, and is bactericidal, all desirable features in a therapeutic antibacterial peptide.

Production Optimization and In Vitro Evaluation of Anti-Proliferative, Anti-Oxidant and Anti-Inflammatory Potential of the Antibacterial Peptide MAFP9

Peptides are important natural bioactive agents obtained from various sources including microbes, plants and animals. The present study involved the optimization and physicochemical characterization of an antibacterial peptide MFAP9 produced by a marine fungus Aspergillus fumigatus BTMF9 and its vitro evaluation of antiproliferative, antioxidant and anti-inflammatory potential. Antiproliferative activity was performed using A549 lung carcinoma and normal L929 fibroblast cell lines employing MTT assay method. Antioxidant activity was assessed using DPPH assay and Cox2 inhibition assay of peptide treated LPS stimulated THP1 cell lines was used for anti-inflammatory studies. The results of in vitro antiproliferative activity assessment showed that MFAP9 was cytotoxic with an IC50 value of 29 µg/mL towards A549 cells. Fluorescence microscopic analysis revealed apoptotic features such as chromatin condensation and alterations in the size and the shape of cells after treatment with MFAP9 at a concentration 50 µg/mL. The DPPH radical scavenging activity of MFAP9 exhibits reasonably higher scavenging activity compared to that of standard antioxidant at same concentration level. Moreover, MFAP9 showed significant anti-inflammatory activities. Time course experiment was conducted with the Czapek- Dox medium and optimized the rate of MFAP9 production. The study on various physico-chemical parameters on the stability revealed that the maximum active temperature of MAFP9 is 50oC, stable in basic pH and 1 mM concentration of Ni2+, Cd2+ and Mg2+ promotes the peptide activity. Hopefully, by employing the advancements in proteomics, bioinformatics, and modification strategies, MFAP9 could emerge as novel promising therapeutic drug in future for various clinical applications.