Alignment‐based design and synthesis of new antimicrobial Aurein‐derived peptides with improved activity against Gram‐negative bacteria and evaluation of their toxicity on human cells

Madanchi, Hamid; Akbari, Shabnam; Shabani, Ali Akbar; Sardari, Soroush; Farahani, Yekta Farmahini; Ghavami, Ghazaleh; Kiasari, Ramin Ebrahimi

doi:10.1002/ddr.21503

Cited by 22 publications

(10 citation statements)

References 27 publications

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“…It has a strong ability of immune regulation and inhibition of TNF-α production from LPS (21). It was reported that when the concentration of AMP was 10-20 μg/mL, it had an excellent bactericidal effect and biological activity (22).…”

Section: Discussionmentioning

confidence: 99%

Antibacterial peptides inhibit MC3T3-E1 cells apoptosis induced by TNF-α through p38 MAPK pathway

Lü

Huan

Liu³

et al. 2020

Ann Transl Med

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Background: Antimicrobial peptides (AMP), as a small molecular polypeptide with a broad antibacterial spectrum and high efficiency, have attracted more and more attention. Few pieces of research on the effect of the antimicrobial peptide on osteoblast under inflammatory conditions have so far been reported. The main aim of this work was to investigate the antiapoptosis effect of the antimicrobial peptide on MC3T3-E1 cells induced by TNF-α and its related mechanism.Methods: Rat MC3T3-E1 cells were co-cultured with different concentrations of antibacterial peptide DP7 and TNF-α.MTS assay, cell scratch test, alkaline phosphatase activity, and alizarin red staining assay were used to determine osteoblast viability in this experiment. Annexin V-FITC/PI double staining cells and flow cytometry were used to analyze apoptosis and Western blot assay detection to show mitogen-activated protein kinase (MAPK) protein expression in rat MC3T3-E1 cells. Then, Realtime polymerase chain reaction (PCR) was used to examine the caspase-3 gene expression. Also, ELISA detection was used to clarify the anti-apoptotic effect of the p38 MAPK inhibitor, SB203580, on cells' apoptosis.Results: Antimicrobial peptide could promote the proliferation, migration, and osteogenic ability of MC3T3-E1 cells induced by TNF-α, but inhibit cell apoptosis rate (P<0.05), and the effect was concentration-dependent. Western blot results showed after TNF-αtreatment, the expression of p-p38 MAPK in the MC3T3-E1 cells increased after TNF-α and antimicrobial peptide cotreatment, TNF-α induced p-p38 MAPK phosphorylation was inhibited, and the difference was statistically significant (P<0.05).Realtime PCR results showed that the gene expression of caspase-3 mRNA was up-regulated after TNF-α treatment, while their expression was down-regulated after cultured with TNF-α and antimicrobial peptide.Elisa's analysis showed that cell apoptosis increased after TNF-α treatment alone, and cell apoptosis was reduced to the normal levels when combined with antimicrobial peptide, and cell apoptosis induced by TNF-α was partially abolished when combined with SB203580.Conclusions: Antimicrobial peptide DP7 could inhibit MC3T3-E1 cells apoptosis induced by TNF-α, and the effect was concentration-dependent. The antiapoptosis activation of the antimicrobial peptide on MC3TE-E1 cells may be related to the inhibition of the p38 MAPK pathway.

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Section: Discussionmentioning

confidence: 99%

Antibacterial peptides inhibit MC3T3-E1 cells apoptosis induced by TNF-α through p38 MAPK pathway

Lü

Huan

Liu³

et al. 2020

Ann Transl Med

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“…All of our final epitopes were in the suitable range in this regard. Increasing the hydrophobic ratio in the non-polar face of the peptides to increase the symmetry in hydrophobic and hydrophilic faces, can enhanced their toxicity and hemolytic activity (Boland and Separovic 2006;Madanchi et al 2019). Helical wheel projection showed that in all epitopes, the hydrophilic face became more discontinuous by polar residues, so the symmetry in hydrophobic and hydrophilic faces was not seen in our epitopes.…”

Section: Antigenmentioning

confidence: 89%

B Cell Epitopes of Four Fimbriae Antigens of Klebsiella pneumoniae: A Comprehensive In Silico Study for Vaccine Development

Zargaran

Akya

Rezaeian

et al. 2020

Int J Pept Res Ther

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Klebsiella pneumoniae is one of the major causes of nosocomial infections worldwide which can cause several diseases in children and adults. The globally dissemination of hyper-virulent strains of K. pneumoniae and the emergence of antibioticsresistant isolates of this pathogen narrows down the treatment options and has renewed interest in its vaccines. Vaccine candidates of Klebsiella pneumoniae have not been adequately protective, safe and globally available yet. In K. pneumoniae infection, it is well known that B cells that induce robust humoral immunity are necessary for the host complete protection. Identifying the B cell epitopes of antigens is valuable to design novel vaccine candidates. In the present study using immunoinformatics approaches we found B cell epitopes of four K. pneumoniae type 1 fimbriae antigens namely FimA, FimF, FimG, and FimH. Linear and conformational B cell epitopes of each antigen were predicted using different programs. Subsequently, many bioinformatics assays were applied to choose the best epitopes including prediction antigenicity, toxicity, human similarity and investigation on experimental records. These assays resulted in final four epitopes (each for one Fim protein). These final epitopes were modeled and their physiochemical properties were estimated to be used as potential vaccine candidates. Altogether, we found four B cell epitopes of K. pneumoniae Fim antigens that are immunogen, antigenic, not similar to human peptides, not allergen and not toxic. Also, they have suitable physiochemical properties to administrate as vaccine, although their complete efficacy should be also shown in vitro and in vivo.

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“…In general, peptides can be modified by the methods of lipidation, glycosylation, and cyclization to enhance their protease resistance and improve their antibacterial activities [ 25 ]. In this case, we designed and synthesized a series of stapled Aurein1.2 peptides that exhibited improved proteolytic stability and higher helical contents than their linear counterparts.…”

Section: Discussionmentioning

confidence: 99%

Design, Synthesis and Antifungal Activity of Stapled Aurein1.2 Peptides

Zheng

Wang²,

Chen

et al. 2021

Antibiotics

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Aurein1.2 is a 13-residue antimicrobial peptide secreted by the Australian tree frog Litoria aurea. In order to improve its stabilities, the helical contents and corresponding biological activities of Aurein1.2 (a series of stapled analogues) were synthesized, and their potential antifungal activities were evaluated. Not surprisingly, the stapled Aurein1.2 peptides showed higher proteolytic stability and helicity than the linear counterpart. The minimum inhibitory concentration (MIC) of ten stapled peptides against six strains of common pathogenic fungi was determined by the microscale broth dilution method recommended by CLSI. Of them, Sau-1, Sau-2, Sau-5, and Sau-9 exhibited better inhibitory effects on the fungi than the linear peptide. These stapled Aurein1.2 peptides may serve as the leading compounds for further optimization and antifungal therapy.

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Alignment‐based design and synthesis of new antimicrobial Aurein‐derived peptides with improved activity against Gram‐negative bacteria and evaluation of their toxicity on human cells

Cited by 22 publications

References 27 publications

Antibacterial peptides inhibit MC3T3-E1 cells apoptosis induced by TNF-α through p38 MAPK pathway

Antibacterial peptides inhibit MC3T3-E1 cells apoptosis induced by TNF-α through p38 MAPK pathway

B Cell Epitopes of Four Fimbriae Antigens of Klebsiella pneumoniae: A Comprehensive In Silico Study for Vaccine Development

Design, Synthesis and Antifungal Activity of Stapled Aurein1.2 Peptides

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