scholarly journals Copper-binding motifs Xxx-His or Xxx-Zzz-His (ATCUN) linked to an antimicrobial peptide: Cu-binding, antimicrobial activity and ROS production

2020 ◽  
Vol 213 ◽  
pp. 111255
Author(s):  
Merwan Bouraguba ◽  
Elise Glattard ◽  
Maxime Naudé ◽  
Rémi Pelletier ◽  
Christopher Aisenbrey ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptide ◽  
Ros Production ◽  
Copper Binding ◽  
Binding Motifs

scholarly journals Comparison of a Short Linear Antimicrobial Peptide with Its Disulfide-Cyclized and Cyclotide-Grafted Variants against Clinically Relevant Pathogens

2021 ◽  
Vol 9 (6) ◽  
pp. 1249
Author(s):  
Johannes Koehbach ◽  
Jurnorain Gani ◽  
Kai Hilpert ◽  
David J Craik
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptide ◽  
Human Serum ◽  
World Health ◽  
Resistant Bacteria ◽  
Moderate Activity ◽  
Antimicrobial Compounds ◽  
Strong Activity ◽  
Linear Peptide ◽  
Linear Version

According to the World Health Organization (WHO) the development of resistance against antibiotics by microbes is one of the most pressing health concerns. The situation will intensify since only a few pharmacological companies are currently developing novel antimicrobial compounds. Discovery and development of novel antimicrobial compounds with new modes of action are urgently needed. Antimicrobial peptides (AMPs) are known to be able to kill multidrug-resistant bacteria and, therefore, of interest to be developed into antimicrobial drugs. Proteolytic stability and toxicities of these peptides are challenges to overcome, and one strategy frequently used to address stability is cyclization. Here we introduced a disulfide-bond to cyclize a potent and nontoxic 9mer peptide and, in addition, as a proof-of-concept study, grafted this peptide into loop 6 of the cyclotide MCoTI-II. This is the first time an antimicrobial peptide has been successfully grafted onto the cyclotide scaffold. The disulfide-cyclized and grafted cyclotide showed moderate activity in broth and strong activity in 1/5 broth against clinically relevant resistant pathogens. The linear peptide showed superior activity in both conditions. The half-life time in 100% human serum was determined, for the linear peptide, to be 13 min, for the simple disulfide-cyclized peptide, 9 min, and, for the grafted cyclotide 7 h 15 min. The addition of 10% human serum led to a loss of antimicrobial activity for the different organisms, ranging from 1 to >8-fold for the cyclotide. For the disulfide-cyclized version and the linear version, activity also dropped to different degrees, 2 to 18-fold, and 1 to 30-fold respectively. Despite the massive difference in stability, the linear peptide still showed superior antimicrobial activity. The cyclotide and the disulfide-cyclized version demonstrated a slower bactericidal effect than the linear version. All three peptides were stable at high and low pH, and had very low hemolytic and cytotoxic activity.

scholarly journals The Designer Antimicrobial Peptide A-hBD-2 Facilitates Skin Wound Healing by Stimulating Keratinocyte Migration and Proliferation

2018 ◽  
Vol 51 (2) ◽  
pp. 647-663 ◽  
Author(s):  
Bobin Mi ◽  
Jing Liu ◽  
Yi Liu ◽  
Liangcong Hu ◽  
Yukun Liu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Wound Healing ◽  
Antimicrobial Peptide ◽  
Structural Stability ◽  
Cell Counting ◽  
Sprague Dawley ◽  
Skin Wound Healing ◽  
High Sodium

Background/Aims: Antimicrobial peptides are effective promoters of wound healing but are susceptible to degradation. In this study, we replaced the GIGDP unit on the N-terminal of the endogenous human antimicrobial peptide hBD-2 with APKAM to produce A-hBD-2 and analyzed the effect on wound healing both in vitro and in vivo. Methods: The effects of A-hBD-2 and hBD-2 on cytotoxicity and proliferation in keratinocytes were assessed by Cell Counting Kit-8 assay. The structural stability and antimicrobial activity of hBD-2 and A-hBD-2 were evaluated against Staphylococcus aureus. RNA and proteins levels were evaluated by real-time PCR and western blotting, respectively. Cell migration was evaluated using a transwell assay. Cell cycle analysis was performed by flow cytometry. Wound healing was assessed in Sprague-Dawley rats. Epidermal thickness was evaluated by hematoxylin and eosin staining. Results: We found that hBD-2 exhibited cytotoxicity at high concentrations and decreased the structural stability in the presence of high sodium chloride concentrations. A-hBD-2 exhibited increased structural stability and antimicrobial activity, and had lower cytotoxicity in keratinocytes. A-hBD-2 increased the migration and proliferation of keratinocytes via phosphorylation of EGFR and STAT3 and suppressed terminal differentiation of keratinocytes. We also found that A-hBD-2 elicited mobilization of intracellular Ca2+ and stimulated keratinocytes to produce pro- and anti-inflammatory cytokines and chemokines via phospholipase C activation. Furthermore, A-hBD-2 promoted wound healing in vivo. Conclusion: Our data suggest that A-hBD-2 may be a promising candidate therapy for wound healing.

scholarly journals 4138 Development of an Antibiofilm Resorbable Membrane for Treating Peri-implantitis

2020 ◽  
Vol 4 (s1) ◽  
pp. 121-121
Author(s):  
Zhou Ye ◽  
Joseph R. Rahimi ◽  
Nicholas G. Fischer ◽  
Hooi Pin Chew ◽  
Conrado Aparicio
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptide ◽  
Statistical Significance ◽  
Oral Bacteria ◽  
Collagen Fibers ◽  
Collagen Membrane ◽  
Type I ◽  
Success Rates ◽  
Hydrophobic Membrane ◽  
Water Contact

OBJECTIVES/GOALS: Peri-implantitis is the inflammation of peri-implant mucosa and subsequent loss of supporting bone. Its treatment is only <40% successful mainly due to persistent bacterial infection. The goal of this project is to increase success rates by developing a robust antibiofilm multi-biomolecular membrane that can be placed around implant surfaces. METHODS/STUDY POPULATION: A collagen membrane was soaked in the antimicrobial peptide GL13K solution overnight to form an interpenetrating fibrillary network. The nanostructure of the membrane was imaged with scanning electron microscope (SEM). The hydrophobicity of the membrane was analyzed by water contact angle (WCA) measurements. The biodegradability was tested in a 0.01 mg/mL Type I collagenase solution for up to 5 weeks. The antimicrobial activity of the membrane was assessed with Gram-positive oral bacteria Streptococcus gordonii. The cytotoxicity was evaluated by culturing human gingival fibroblasts (HGF), and the osteogenesis was assessed using preosteoblasts MC3T3. Pure collagen membrane was used as the control. Statistical significance (p<0.05) was determined by one-way ANOVA with Tukey’s HSD test. RESULTS/ANTICIPATED RESULTS: The antimicrobial peptide GL13K self-assembled to short fibrils (< 1 µm long), which entangled with the larger collagen fibers (around 200 nm in diameter). The collagen fibers presented characteristic periodic banding structures, which provided biomimetic cues for cell behavior as extracellular matrix. The interpenetrated GL13K fibrils turned the highly hydrophilic collagen membrane to a hydrophobic membrane (WCA = 135 °) and significantly reduced the rate of degradation by collagenases. The developed membrane was efficient in preventing the attachment of S. gordonii. A large portion of the attached bacteria was killed on the surface of the membrane. The incorporation of GL13K did not affect the cytocompatibility of the membrane for HGF. DISCUSSION/SIGNIFICANCE OF IMPACT: We developed an antibiofilm membrane with interpenetrating collagen and antimicrobial peptide fibrils. The strong antimicrobial activity and low cytotoxicity support its further translational evaluation as scaffolds for increasing success rate in treating peri-implantitis.

Antimicrobial activity and self-assembly behavior of antimicrobial peptide chensinin-1b with lipophilic alkyl tails

2018 ◽  
Vol 150 ◽  
pp. 546-558 ◽  
Author(s):  
Weibing Dong ◽  
Ziang Liu ◽  
Liying Sun ◽  
Cui Wang ◽  
Yue Guan ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptide ◽  
Self Assembly ◽  
Assembly Behavior

scholarly journals Effects of Dimerization on the Structure and Biological Activity of Antimicrobial Peptide Ctx-Ha

2012 ◽  
Vol 56 (6) ◽  
pp. 3004-3010 ◽  
Author(s):  
E. N. Lorenzón ◽  
G. F. Cespedes ◽  
E. F. Vicente ◽  
L. G. Nogueira ◽  
T. M. Bauab ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Biological Activity ◽  
Antimicrobial Peptide ◽  
Hemolytic Activity ◽  
Pore Diameter ◽  
Solid Phase ◽  
Biological Activities ◽  
Solid Phase Peptide Synthesis ◽  
Activity Assay ◽  
Growth Of Bacteria

ABSTRACTIt is well known that cationic antimicrobial peptides (cAMPs) are potential microbicidal agents for the increasing problem of antimicrobial resistance. However, the physicochemical properties of each peptide need to be optimized for clinical use. To evaluate the effects of dimerization on the structure and biological activity of the antimicrobial peptide Ctx-Ha, we have synthesized the monomeric and three dimeric (Lys-branched) forms of the Ctx-Ha peptide by solid-phase peptide synthesis using a combination of 9-fluorenylmethyloxycarbonyl (Fmoc) andt-butoxycarbonyl (Boc) chemical approaches. The antimicrobial activity assay showed that dimerization decreases the ability of the peptide to inhibit growth of bacteria or fungi; however, the dimeric analogs displayed a higher level of bactericidal activity. In addition, a dramatic increase (50 times) in hemolytic activity was achieved with these analogs. Permeabilization studies showed that the rate of carboxyfluorescein release was higher for the dimeric peptides than for the monomeric peptide, especially in vesicles that contained sphingomyelin. Despite different biological activities, the secondary structure and pore diameter were not significantly altered by dimerization. In contrast to the case for other dimeric cAMPs, we have shown that dimerization selectively decreases the antimicrobial activity of this peptide and increases the hemolytic activity. The results also show that the interaction between dimeric peptides and the cell wall could be responsible for the decrease of the antimicrobial activity of these peptides.

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