Host defence peptides (HDPs) are integral components of innate immunity across all living organisms. These peptides can exert direct antibacterial effects, targeting planktonic cells (referred to as antimicrobial peptides), and exhibit antibiofilm (referred to as antibiofilm peptides), antiviral, antifungal and host-directed immunomodulatory activities. In this Review, we discuss how the complex functional attributes of HDPs provide many opportunities for the development of antimicrobial therapeutics, focusing particularly on their emerging antibiofilm properties. The mechanisms of action of antibiofilm peptides are compared and contrasted with those of antimicrobial peptides. Furthermore, obstacles for the practical translation of candidate peptides into therapeutics and the potential solutions are discussed. Critically, HDPs have the value-added assets of complex functional attributes, particularly antibiofilm and anti-inflammatory activities and their synergy with conventional antibiotics.

01 Feb 2021·Applied Microbiology and BiotechnologyQ3 · ENGINEERING & TECHNOLOGY

Antibiofilm peptides as a promising strategy: comparative research

Q3 · ENGINEERING & TECHNOLOGY

Article

Author: Lin, Huancai ; Li, Jing ; Chen, Dongru

Biofilms lead to approximately 65% of infections, and these infections are hard to treat. Thus, it is crucial to identify effective antibiofilm agents with low cytotoxicity. Peptides with antibiofilm activity have been regarded as promising solutions, and peptides with MBICs (minimal biofilm inhibitory concentrations) that are lower than their minimal inhibitory concentration (MICs) (minimal inhibitory concentrations) are appealing. Therefore, we systematically summarized and classified previously reported peptides with antibiofilm activity. A total of 51 peptides with antibiofilm activity were classified into 14 categories. The MICs and MBICs of these fourteen representative peptides, one selected from each category, were compared against the Gram-positive bacterium Streptococcus mutans, the Gram-negative bacterium Pseudomonas aeruginosa, and the fungus Candida albicans. Six representative peptides (C5-pleurocidin, C6-Pac-525, C9-protegrin-1, C11-TetraF2W-RR, C13-WLBU2, and C14-melittin) showed antibiofilm activity against both bacteria and fungi, and among these 6 representative peptides, 4 peptides (C9-protegrin-1, C11-TetraF2W-RR, C13-WLBU2, and C14-melittin) could prevent biofilm formation with lower MBIC values than their MICs. CLSM (confocal laser scanning microscopy), SEM (scanning electron microscopy), and TEM (transmission electron microscopy) were further used to observe the morphologies of the biofilms after treatment with the peptides. Among the above 4 peptides, WLBU2 and melittin sparsely scattered the biofilms without destroying the bacteria. In conclusion, the currently reported peptides with antibiofilm activity are limited in number, but peptides with lower MBICs than MICs exist as promising candidates against biofilm-related infections and need further study. KEY POINTS: • Antibiofilm peptides could inhibit biofilm formation with MBICs that are lower than MICs. • The mechanism of antibiofilm peptides is not only due to antimicrobial activity.

01 Jan 2021·Dental MaterialsQ1 · ENGINEERING & TECHNOLOGY

Peptide decorated demineralized dentin matrix with enhanced bioactivity, osteogenic differentiation via carboxymethyl chitosan

Q1 · ENGINEERING & TECHNOLOGY

Article

Author: Nie, Li ; Li, Xinyue ; Xie, Bingwu ; Jing, Xueqin ; Li, Conghua ; Dai, Youli

OBJECTIVESTo improve the biocompatibility and osteogenic activity of demineralized dentin matrix (DDM) by grafting peptides on its surface.METHODSDDM was obtained by pulverizing extracted human teeth that had been systematically demineralized and dried. Four groups of materials were evaluated: DDM, DDM/carboxymethyl chitosan (CMC), DDM/CMC/bone forming peptide-1 (BFP-1), and blank. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR) and fluorescence localization were used to characterize the surface of the DDM materials. Cell viability was assessed using a CCK8 assay, scanning electron microscopy (SEM) and in vitro osteogenesis was analyzed using real-time RT-PCR (RT-qPCR) and Alizarin red and alkaline phosphatase staining. Three different materials were implanted into mandibular bone defects in rats. After 8 weeks, bone regeneration was assessed by histomorphometry of HE-stained slides.RESULTSFT-IR, XPS, and fluorescence microscopy demonstrated that the DDM surfaces were successfully modified with BFP-1. The CCK8 assay indicated that the proliferation of cells is higher on the DDM/CMC/BFP-1 material than on DDM or DDM/CMC (P < 0.05). Cells were more likely to adhere to DDM/CMC/BFP-1, as observed by SEM. Greater in vitro osteogenesis was observed in the DDM/CMC/BFP-1 group which displayed stronger alkaline phosphatase activity, more alizarin red-stained nodules, and higher target gene expression, as detected by RT-qPCR (P＜0.05). HE staining of in vivo explants indicated that greater quantities of new bone had formed in the DDM/CMC/BFP-1 group.SIGNIFICANCECompared with DDM, DDM/CMC/BFP-1 exhibited superior biocompatibility and osteogenesis, using a method of surface modification that has great potential for future clinical use.

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Indication	Highest Phase	Country/Location	Organization	Date
Bone and joint infections	Discovery	FR	Biofilm PharmaStartup	-
Diabetic Foot	Discovery	FR	Biofilm PharmaStartup	-
Staphylococcal Infections	Discovery	FR	Biofilm PharmaStartup	-

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