Abstract
Following our previous study as the first study of the antifungal effect of CE-MA peptide and its truncated derivatives (CMt1–CMt3) against fungal strains Candida albicans, Candida glabrata, Aspergillus fumigatus, and Microsporum canis, in this study, the antimicrobial effects of CE-MA antimicrobial peptide and its truncated derivatives were evaluated against new fungal strains and specific strains of bacteria. Next, the cytotoxicity of synthetic peptides against L929 cells, the killing kinetics, and their action mechanism against bacteria was determined. The results showed that CE-MA and its derivatives had no antibacterial effect against Gram-positive bacteria. However, CMt1 with ten amino acids has the best antifungal and antibacterial effects, while CMt3 has the weakest antimicrobial effect. CMt1 also has a toxicity of less than 10% against L929 cells. CE-MA and CMt1 exert their antimicrobial effects by binding to LPS from the cell membranes of Gram-negative bacteria. Our present and previous studies about CE-MA peptide and its truncated derivatives show that if truncation is performed correctly, it can be a good strategy for reducing toxicity, allergenicity, inflammatory effects, synthesis costs, and increasing the stability of AMPs.
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References
Abastabar M, Haghani I, Ahangarkani F et al (2019) Candida auris otomycosis in Iran and review of recent literature. Mycoses 62:101–105. https://doi.org/10.1111/myc.12886
Ahmadi K, Farasat A, Rostamian M et al (2021) Enfuvirtide, an HIV-1 fusion inhibitor peptide, can act as a potent SARS-CoV-2 fusion inhibitor: an in silico drug repurposing study. J Biomol Struct Dyn. https://doi.org/10.1080/07391102.2021.1871958
Ashwini S, Varkey S, Shantarum M (2017) In silico docking of polyphenolic compounds against caspase 3-hela cell line protein. Int J Drug Dev Res 9:28–32
Boman HG (2003) Antibacterial peptides: basic facts and emerging concepts. J Intern Med 254:197–215. https://doi.org/10.1046/j.1365-2796.2003.01228.x
Gaspar D, Veiga AS, Castanho MARB (2013) From antimicrobial to anticancer peptides. A Review Front Microbiol. https://doi.org/10.3389/fmicb.2013.00294
Harika M, Kumar T, Reddy L (2017) Docking studies of benzimidazole derivatives using hex 8.0. Int J Pharm Sci Res 8:1677
Huan Y, Kong Q, Mou H, Yi H (2020) Antimicrobial peptides: classification, design, application and research progress in multiple fields. Front Microbiol. https://doi.org/10.3389/fmicb.2020.582779
Kang M, Yoon H, Choi Y (2017) RIPL peptide as a novel cell-penetrating and homing peptide: design, characterization, and application to liposomal nanocarriers for hepsin-specific intracellular drug delivery. Nanostructures Cancer Ther. https://doi.org/10.1016/B978-0-323-46144-3.00005-2
Lee E, Shin A, Kim Y (2015) Anti-inflammatory activities of Cecropin a and its mechanism of action. Arch Insect Biochem Physiol 88:31–44. https://doi.org/10.1002/arch.21193
Liu Z, Brady A, Young A et al (2007) Length effects in antimicrobial peptides of the (RW) n series. Antimicrob Agents Chemother 51:597–603. https://doi.org/10.1128/AAC.00828-06
Madanchi H, Akbari S, Shabani AA et al (2019a) 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. Drug Dev Res 80:162–170. https://doi.org/10.1002/ddr.21503
Madanchi H, Khalaj V, Jang S et al (2019) AurH1: a new heptapeptide derived from Aurein 1.2 antimicrobial peptide with specific and exclusive fungicidal activity. J Pept Sci. https://doi.org/10.1002/psc.3175
Madanchi H, Ebrahimi Kiasari R, Seyed Mousavi SJ et al (2020a) Design and synthesis of lipopolysaccharide-binding antimicrobial peptides based on truncated rabbit and human cap18 peptides and evaluation of their action mechanism. Probiotics Antimicrob Proteins 12:1582–1593. https://doi.org/10.1007/s12602-020-09648-5
Madanchi H, Sardari S, Shajiee H et al (2020b) Design of new truncated derivatives based on direct and reverse mirror repeats of first six residues of Caerin 4 antimicrobial peptide and evaluation of their activity and cytotoxicity. Chem Biol Drug Des 96:801–811. https://doi.org/10.1111/cbdd.13689
Maisetta G, Di Luca M, Esin S et al (2008) Evaluation of the inhibitory effects of human serum components on bactericidal activity of human beta defensin 3. Peptides 29:1–6. https://doi.org/10.1016/j.peptides.2007.10.013
Memariani H, Shahbazzadeh D, Sabatier J-M et al (2016) Mechanism of action and in vitro activity of short hybrid antimicrobial peptide PV3 against Pseudomonas aeruginosa. Biochem Biophys Res Commun 479:103–108. https://doi.org/10.1016/j.bbrc.2016.09.045
Michael Conlon J, Mechkarska M, King JD (2012) Host-defense peptides in skin secretions of African clawed frogs (Xenopodinae, Pipidae). Gen Comp Endocrinol 176:513–518. https://doi.org/10.1016/j.ygcen.2011.10.010
Namvar Erbani S, Madanchi H, Ajodani far H, et al (2021) First report of antifungal activity of CecropinA-Magenin2 (CE-MA) hybrid peptide and its truncated derivatives. Biochem Biophys Res Commun 549:157–163. https://doi.org/10.1016/j.bbrc.2021.02.106
Peters BM, Shirtliff ME, Jabra-Rizk MA (2010) Antimicrobial peptides: primeval molecules or future drugs? PLoS Pathog 6:e1001067. https://doi.org/10.1371/journal.ppat.1001067
Shin SY, Kang JH, Lee MK et al (1998) Cecropin a - magainin 2 hybrid peptides having potent antimicrobial activity with low hemolytic effect. IUBMB Life 44:1119–1126. https://doi.org/10.1080/15216549800202192
Silva PM, Gonçalves S, Santos NC (2014) Defensins: antifungal lessons from eukaryotes. Front Microbiol. https://doi.org/10.3389/fmicb.2014.00097
Silvestro L, Weiser JN, Axelsen PH (2000) Antibacterial and antimembrane activities of Cecropin A in Escherichia coli. Antimicrob Agents Chemother 44:602–607. https://doi.org/10.1128/AAC.44.3.602-607.2000
Szilágyi A, Skolnick J (2006) Efficient prediction of nucleic acid binding function from low-resolution protein structures. J Mol Biol 358:922–933. https://doi.org/10.1016/j.jmb.2006.02.053
Wang G (2014) Human Antimicrobial Peptides and Proteins. Pharmaceuticals 7:545–594. https://doi.org/10.3390/ph7050545
Xu W, Zhu X, Tan T et al (2014) Design of embedded-hybrid antimicrobial peptides with enhanced cell selectivity and anti-biofilm activity. PLoS ONE 9:e98935. https://doi.org/10.1371/journal.pone.0098935
Zhao D, Lu K, Liu G et al (2020) PEP-FOLD design, synthesis, and characteristics of finger-like polypeptides. Spectrochim Acta Part A Mol Biomol Spectrosc 224:117401. https://doi.org/10.1016/j.saa.2019.117401
Acknowledgements
We would like to thank the staff of the School of medicine, Department, and Center for Biotechnology Research from Semnan University of Medical Sciences and Drug Design and Bioinformatics Unit of Pasteur Institute of Iran.
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Hamid Madanchi contributed to the study's conception and design. Material preparation, data collection, and analysis were performed by Hamid Madanchi, Samaneh Namvar Erbani, Hatef Ajoudanifar, and Ali Akbar Shabani. The first draft of the manuscript was written by Hamid Madanchi. All authors read and approved the final manuscript.
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Hamid Madanchi and Hatef Ajoudanifar are co-corresponding authors.
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Namvar Arabani, S., Madanchi, H., Ajoudanifar, H. et al. Evaluation of Antibacterial, Antifungal, and Cytotoxicity Effects of CecropinA-Magenin2 (CE-MA) Peptide and Its Truncated Derivatives and Study of Their Action Mechanism. Int J Pept Res Ther 28, 126 (2022). https://doi.org/10.1007/s10989-022-10433-x
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DOI: https://doi.org/10.1007/s10989-022-10433-x