Controversy Between In Vitro Biological Activities of a Novel Designed Antimicrobial Peptide and Its In Silico Predicted Activities Novel in silico designed AMP
Trends in Peptide and Protein Sciences,
Vol. 7 (2022),
7 March 2022
,
Page 1-12 (e4)
https://doi.org/10.22037/tpps.v7i.38346
Abstract
Due to their unique mechanisms of action, antimicrobial peptides (AMPs) are promising candidates to combat different infectious diseases. They usually non-specifically interact with the bacterial cell membrane, create pores in their membrane and increase its permeability which causes the death of pathogens. In the design and development of AMPs, in silico strategies have been developed to enhance the function and activity of natural peptides. In this study, in silico approaches were used to develop a novel AMP with several extra bioactivities. Then, the designed AMP were analyzed through computational methods by in vitro experiments. Bioinformatics research revealed a 10-amino-acid peptide (LVSARIRCPK) having antibacterial, anti-biofilm, antiviral, antifungal, and anti-inflammatory effects. However, only the antiviral capabilities of the peptide were validated in the experimental analysis of antibacterial, antifungal, and antiviral activities. This data suggests that; while bioinformatics approaches have greatly advanced in recent years, more optimization work has to be done in order to attain high accuracy and minimize mistakes.
HIGHLIGHTS
- A novel 10 residues anti-microbial peptide was designed using bioinformatics tools.
- In vitro analysis showed that this novel AMP did not have efficient antimicrobial activities.
- Stringencies of bioinformatics criteria thresholds setting may result in better design.
- Antimicrobial peptides
- In silico design
- Antiviral activity
- Antibacterial activity
- Antifungal activity
How to Cite
References
Alsaggar, M., Al-Tarawneh, A., Al Tall, Y. and M. Al-Hazabreh, (2022). "SAMA peptide, a rationally designed antimicrobial peptide." Journal of Applied Pharmaceutical Science, 12(01): 182-189; DOI: https://doi.org/10.7324/JAPS.2021.120118.
Bahar, A.A. and D. Ren, (2013). "Antimicrobial peptides." Pharmaceuticals, 6(12): 1543-1575; DOI:https://doi.org/10.3390/ph6121543.
Balouiri, M., Sadiki, M. and S.K. Ibnsouda, (2016). "Methods for in vitro evaluating antimicrobial activity: A review." Journal of Pharmaceutical Analysis, 6(2): 71-79; DOI: https://doi.org/10.1016/j.jpha.2015.11.005.
Cardoso, M.H., Orozco, R.Q., Rezende, S.B., Rodrigues, G., Oshiro, K.G.N., Cândido, E.S. and O.L. Franco, (2020). "Computer-aided design of antimicrobial peptides: Are we generating effective drug candidates?" Frontiers in Microbiology, 10: 3097; DOI: https://doi.org/10.3389/fmicb.2019.03097.
Cash Heather, L., Whitham Cecilia, V., Behrendt Cassie, L. and V. Hooper Lora, (2006). "Symbiotic bacteria direct expression of an intestinal bactericidal lectin." Science, 313(5790): 1126-1130; DOI: https://doi.org/10.1126/science.1127119.
Chaudhary, K., Kumar, R., Singh, S., Tuknait, A., Gautam, A., Mathur, D., Anand, P., Varshney, G.C. and G.P.S. Raghava, (2016). "A web server and mobile app for computing hemolytic potency of peptides." Scientific Reports, 6(1): 22843; DOI: https://doi.org/10.1038/srep22843.
Chegini, P.P., Nikokar, I., Hosseinabadi, T. and M. Tabarzad, (2017). "Concerns in the design and development of novel antimicrobial peptides." Trends in Peptide and Protein Sciences, 1(4): 135-143; DOI: https://doi.org/10.22037/tpps.v1i4.16328.
Chegini, P.P., Nikokar, I., Tabarzad, M., Faezi, S. and A. Mahboubi, (2019). "Effect of amino acid substitutions on biological activity of antimicrobial peptide: design, recombinant production, and biological activity." Iranian Journal of Pharmaceutical Research: IJPR, 18(Suppl1): 157-168; DOI: https://doi.org/10.22037/ijpr.2019.112397.13734 .
Chou, S., Li, Q., Wu, H., Li, J., Chang, Y.-F., Shang, L., Li, J., Wang, Z. and A. Shan, (2021). "Selective antifungal activity and fungal biofilm inhibition of tryptophan center symmetrical short peptide." International Journal of Molecular Sciences, 22(15): 8231; DOI: https://doi.org/10.3390/ijms22158231.
Cipcigan, F., Carrieri, A.P., Pyzer-Knapp, E.O., Krishna, R., Hsiao, Y.-W., Winn, M., Ryadnov, M.G., Edge, C., Martyna, G. and J. Crain, (2018). "Accelerating molecular discovery through data and physical sciences: Applications to peptide-membrane interactions." The Journal of Chemical Physics, 148(24): 241744; DOI: https://doi.org/10.1063/1.5027261.
Cornaglia, G. (2009). "Fighting infections due to multidrug-resistant gram-positive pathogens." Clinical Microbiology and Infection, 15(3): 209-211; DOI: https://doi.org/10.1111/j.1469-0691.2009.02737.x.
Deléage, G. and B. Roux, (1987). "An algorithm for protein secondary structure prediction based on class prediction." Protein Engineering, Design and Selection, 1(4): 289-294; DOI: https://doi.org/10.1093/protein/1.4.289.
Fathi, F., Ghobeh, M. and M. Tabarzad, (2022). "Anti-microbial peptides: Strategies of design and development and their promising wound-healing activities." Molecular Biology Reports, in press; DOI: https://doi.org/10.1007/s11033-022-07405-1.
Fry, D.E. (2018). "Antimicrobial peptides." Surgical Infections, 19(8): 804-811; DOI: https://doi.org/10.1089/sur.2018.194.
Gautam, A., Chaudhary, K., Kumar, R. and G.P.S. Raghava, (2015). "Computer-aided virtual screening and designing of cell-penetrating peptides. " In: Cell-Penetrating Peptides Methods in Molecular Biology, Langel Ü. (ed), Humana Press, New York, NY. 1324: pp.59-69; DOI: https:// doi: 10.1007/978-1-4939-2806-4_4.
Gautier, R., Douguet, D., Antonny, B. and G. Drin, (2008). "HELIQUEST: a web server to screen sequences with specific α-helical properties." Bioinformatics, 24(18): 2101-2102; DOI: https://doi.org/10.1093/bioinformatics/btn392
Ge, L., Chen, X., Ma, C., Zhou, M., Xi, X., Wang, L., Ding, A., Duan, J., Chen, T. and C. Shaw (2014). "Balteatide: A novel antimicrobial decapeptide from the skin secretion of the purple-sided leaf frog, Phyllomedusa baltea." The Scientific World Journal, 2014: 176214; DOI: https://doi.org/10.1155/2014/176214.
Ghosh, S.K. and A. Weinberg, (2021). "Ramping up antimicrobial peptides against severe acute respiratory syndrome Coronavirus-2." Frontiers in Molecular Biosciences, 8: 620806-620806. DOI: https://doi.org/10.3389/fmolb.2021.620806.
Gupta, S., Kapoor, P., Chaudhary, K., Gautam, A., Kumar, R. and G.P.S. Raghava, (2013). "In silico approach for predicting toxicity of peptides and proteins." PLOS ONE, 8(9): e73957; DOI: https://doi: 10.1371/journal.pone.0073957. eCollection 2013.
Huang, Y., Huang, J. and Y. Chen, (2010). "Alpha-helical cationic antimicrobial peptides: relationships of structure and function." Protein and Cell, 1(2): 143-152; DOI: https://doi: 10.1007/s13238-010-0004-3. Epub 2010 Feb 6.
Jorgensen, J.H. and M.J. Ferraro, (2009). "Antimicrobial susceptibility testing: a review of general principles and contemporary practices." Clinical Infectious Diseases, 49(11): 1749-1755; DOI: https:// doi: 10.1086/647952.
Kim, H., Jang, J.H., Kim, S.C. and J.H. Cho, (2014). "De novo generation of short antimicrobial peptides with enhanced stability and cell specificity." Journal of Antimicrobial Chemotherapy, 69(1): 121-132; DOI: https:// doi: 10.1093/jac/dkt322. Epub 2013 Aug 14.
Klubthawee, N., Adisakwattana, P., Hanpithakpong, W., Somsri, S. and R. Aunpad, (2020). "A novel, rationally designed, hybrid antimicrobial peptide, inspired by cathelicidin and aurein, exhibits membrane-active mechanisms against Pseudomonas aeruginosa." Scientific Reports, 10(1): 9117. 1-17; DOI: https://doi.org/10.1038/s41598-020-65688-5.
Koo, H. B. and J. Seo, (2019). "Antimicrobial peptides under clinical investigation." Peptide Science, 111(5): e24122; DOI: https://doi.org/10.1002/pep2.24122.
Kumar, P., Kizhakkedathu, J.N. and S.K. Straus, (2018). "Antimicrobial peptides: diversity, mechanism of action and strategies to improve the activity and biocompatibility in vivo." Biomolecules, 8(1): 1-24; DOI: https:// doi: 10.3390/biom8010004.
Lamiable, A., Thévenet, P., Rey, J., Vavrusa, M., Derreumaux, P. and P. Tufféry, (2016). "PEP-FOLD3: faster de novo structure prediction for linear peptides in solution and in complex." Nucleic Acids Research, 44(W1): W449-W454; DOI: https:// doi: 10.1093/nar/gkw329.
Le, C.-F., Yusof, M.Y.M., Hassan, H. and S.D. Sekaran, (2015). "In vitro properties of designed antimicrobial peptides that exhibit potent antipneumococcal activity and produces synergism in combination with penicillin." Scientific Reports, 5(1): 9761: 1-8; DOI: https://doi.org/10.1038/srep09761
Liu, S., Bao, J., Lao, X. and H. Zheng, (2018). "Novel 3D structure based model for activity prediction and design of antimicrobial peptides." Scientific Reports, 8(1): 11189. 1-12; DOI: https://doi:10.1038/s41598-018-29566-5.
Madeira, F., Pearce, M., Tivey, A., Basutkar, P., Lee, J., Edbali, O., Madhusoodanan, N., Kolesnikov, A. and R. Lopez, (2022). "Search and sequence analysis tools services from EMBL-EBI in 2022." Nucleic Acids Research, gkac240: 1-4; DOI: https://doi: 10.1093/nar/gkac240.
Magana, M., Pushpanathan, M., Santos, A.L., Leanse, L., Fernandez, M., Ioannidis, A., Giulianotti, M.A., Apidianakis, Y., Bradfute, S., Ferguson, A.L., Cherkasov, A., Seleem, M.N., Pinilla, C., de la Fuente-Nunez, C., Lazaridis, T., Dai, T., Houghten, R.A., Hancock, R.E.W. and G.P. Tegos, (2020). "The value of antimicrobial peptides in the age of resistance." The Lancet Infectious Diseases, 20(9): e216-e230; DOI: https:// 10.1016/s1473-3099(20)30327-3.
Manavalan, B., Shin, T.H., Kim, M.O. and G. Lee, (2018). "AIPpred: Sequence-based prediction of anti-inflammatory peptides using random forest." Frontiers in Pharmacology, 9 (276): 1-12; DOI: https:// doi: 10.3389/fphar.2018.00276.
Meher, P.K., Sahu, T.K., Saini, V. and A.R. Rao, (2017). "Predicting antimicrobial peptides with improved accuracy by incorporating the compositional, physico-chemical and structural features into Chou’s general PseAAC." Scientific Reports, 7(1): 42362; DOI: https://doi: 10.1038/srep42362.
Molero-Abraham, M., Glutting, J.-P., Flower, D.R., Lafuente, E.M. and P.A. Reche, (2015). "EPIPOX: Immunoinformatic characterization of the shared T-cell epitome between Variola virus and related pathogenic orthopoxviruses." Journal of Immunology Research 2015(738020): 1-11; DOI: http://dx.doi.org/10.1155/2015/738020.
Mookherjee, N., Anderson, M.A., Haagsman, H.P. and D.J. Davidson, (2020). "Antimicrobial host defence peptides: functions and clinical potential." Nature Reviews Drug Discovery, 19(5): 311-332; DOI: https://doi.org/10.1038/s41573-019-0058-8.
Moretta, A., Scieuzo, C., Petrone, A.M., Salvia, R., Manniello, M.D., Franco, A., Lucchetti, D., Vassallo, A., Vogel, H. and A. Sgambato, (2021). "Antimicrobial peptides: A new hope in biomedical and pharmaceutical fields." Frontiers in Cellular and Infection Microbiology 11(668632): 1-26; DOI: https://doi: 10.3389/fcimb.2021.668632.
Mustafa, S., Balkhy, H. and M. Gabere, (2019). "Peptide-protein interaction studies of antimicrobial peptides targeting middle east respiratory syndrome Coronavirus spike protein: An in silico approach." Advances in Bioinformatics, 2019(6815105): 1-16; DOI: https:// doi: 10.1155/2019/6815105.
Neff, J.A., Bayramov, D.F., Patel, E.A. and J. Miao, (2020). "Novel antimicrobial peptides formulated in chitosan matrices are effective against biofilms of multidrug-resistant wound pathogens." Military Medicine, 185: 637-643; DOI: https://doi.org/10.1093/milmed/usz222.
Oliveira, N. G. J., M. H. Cardoso, N. Velikova, M. Giesbers, J. M. Wells, T. M. B. Rezende, R. de Vries and O. L. Franco, (2020). "Physicochemical-guided design of cathelicidin-derived peptides generates membrane active variants with therapeutic potential." Scientific Reports, 10(1): 9127.1-13; DOI: https://doi.org/10.1038/s41598-020-66164-w.
Papo, N. and Y. Shai, (2005). "Host defense peptides as new weapons in cancer treatment." Cellular and Molecular Life Sciences: CMLS, 62(7): 784-790; DOI: https:// doi: 10.1556/MOnkol.54.2010.1.7.
Patrulea, V., Borchard, G. and O. Jordan, (2020). "An update on antimicrobial peptides (AMPs) and their delivery strategies for wound infections." Pharmaceutics, 12(9): 1-39; DOI: https:doi:10.3390/pharmaceutics12090840.
Patrulea, V., Younes, I., Jordan, O. and G. Borchard, (2019). Chitosan-based systems for controlled delivery of antimicrobial peptides for biomedical application. In: Functional Chitosan, Jana, S. and S. Jana, (eds). Springer, Singapore: pp. 415-455; DOI: https://doi: 10.1007/978-981-15-0263-7_14.
Pedron, C.N., Torres, M.D.T., Lima, J.A.S., Silva, P.I., Silva, F.D. and V.X. Oliveira, (2017). "Novel designed VmCT1 analogs with increased antimicrobial activity." European Journal of Medicinal Chemistry, 126: 456-463; DOI: https:// doi: 10.1016/j.ejmech.2016.11.040. Epub 2016 Nov 24.
Ramezanzadeh, M., Saeedi, N., Mesbahfar, E., Farrokh, P., Salimi, F. and A. Rezaei, (2021). "Design and characterization of new antimicrobial peptides derived from aurein 1.2 with enhanced antibacterial activity." Biochimie, 181: 42-51; DOI: https://doi.org/10.1016/j.biochi.2020.11.020.
Schaduangrat, N., Nantasenamat, C., Prachayasittikul, V. and W. Shoombuatong, (2019). "Meta-iAVP: A Sequence-based meta-predictor for improving the prediction of antiviral peptides using effective feature representation." International Journal of Molecular Sciences, 20(22): 1-25; DOI: https://doi:10.3390/ijms20225743.
Shankar, P.R. (2016). "Book review: tackling drug-resistant infections globally." Archives of Pharmacy Practice, 7(3): 110-111; DOI: https:// doi:10.4103/2045-080X.186181.
Sharma, A., Gupta, P., Kumar, R. and A. Bhardwaj (2016). "dPABBs: A Novel in silico approach for predicting and designing anti-biofilm peptides." Scientific Reports 6(1): 21839. 1-13; DOI: https://doi: 10.1038/srep21839.
Sonesson, A., Nordahl, E.A., Malmsten, M. and A. Schmidtchen, (2011). "Antifungal activities of peptides derived from domain 5 of high-molecular-weight kininogen." International Journal of Peptides, 2011: 761037.1-11; DOI: https://doi:10.1155/2011/761037.
Souza, P.F.N., Marques, L.S.M., Oliveira, J.T.A., Lima, P.G., Dias, L.P., Neto, N.A.S., Lopes, F.E.S., Sousa, J.S., Silva, A.F.B., Caneiro, R.F., Lopes, J.L.S., Ramos, M.V. and C.D.T. Freitas, (2020). "Synthetic antimicrobial peptides: From choice of the best sequences to action mechanisms." Biochimie, 175: 132-145; DOI: https://doi.org/10.1016/j.biochi.2020.05.016.
The UniProt Consortium, (2021). "UniProt: the universal protein knowledgebase in 2021." Nucleic Acids Research, 49(D1): D480-D489; DOI: https:// doi:10.1093/nar/gkaa1100.
Thompson, A. H., Bjourson, A. J., Orr, D. F., Shaw, C. and S. McClean, (2007). "Amphibian skin secretomics: application of parallel quadrupole time-of-flight mass spectrometry and peptide precursor cDNA cloning to rapidly characterize the skin secretory peptidome of Phyllomedusa hypochondrialis azurea: discovery of a novel peptide family, the hyposins." Journal of Proteome Research, 6(9): 3604-3613. DOI: https:// doi: 10.1021/pr0702666. Epub 2007 Aug 14.
Tincho, M. B., Morris, T., Meyer, M. and A. Pretorius, (2020). "Antibacterial activity of rationally designed antimicrobial peptides." International Journal of Microbiology, 2020 (2131535): 1-9; DOI: https://doi.org/10.1155/2020/2131535.
Ting, D. S. J., Beuerman, R. W., Dua, H. S., Lakshminarayanan, R. and I. Mohammed, (2020). "Strategies in translating the therapeutic potentials of host defense peptides." Frontiers in Immunology, 11(983): 1-16; DOI: https://doi.org/10.3389/fimmu.2020.00983.
van der Weide, H., J. Brunetti, A. Pini, L. Bracci, C. Ambrosini, P. Lupetti, E. Paccagnini, M. Gentile, A. Bernini, N. Niccolai, D. V.-d. Jongh, I. A. J. M. Bakker-Woudenberg, W. H. F. Goessens, J. P. Hays and C. Falciani, (2017). "Investigations into the killing activity of an antimicrobial peptide active against extensively antibiotic-resistant K. pneumon iae and P. aeruginosa." Biochimica et Biophysica Acta (BBA) - Biomembranes 1859(10): 1796-1804. DOI: https:// doi: 10.1016/j.bbamem.2017.06.001. Epub 2017 Jun 3.
Waghu, F. H. and S. Idicula-Thomas, (2020). "Collection of antimicrobial peptides database and its derivatives: Applications and beyond." Protein Science, 29(1): 36-42; DOI: https://doi.org/10.1002/pro.3714.
Wang, G., X. Li and Z. Wang (2015). "APD3: the antimicrobial peptide database as a tool for research and education." Nucleic Acids Research, 44(D1): D1087-D1093; DOI: https:// doi: 10.1093/nar/gkv1278. Epub 2015 Nov 23.
Xu, H., Iyer, N., Huettner, J. E. and S. E. Sakiyama-Elbert, (2015). "A puromycin selectable cell line for the enrichment of mouse embryonic stem cell-derived V3 interneurons." Stem Cell Research & Therapy, 6(1): 220. 1-17; DOI: https://doi.org/10.1186/s13287-015-0213-z.
Xu, W., Zhu, X., Tan, T., Li, W. and A. Shan, (2014). "Design of embedded-hybrid antimicrobial peptides with enhanced cell selectivity and anti-biofilm activity." PLOS ONE, 9(6): e98935; DOI: https://doi.org/10.1371/journal.pone.0098935.
Yeaman, M. R. and N. Y. Yount, (2003). "Mechanisms of antimicrobial peptide action and resistance." Pharmacological Reviews, 55(1): 27-55; DOI: https:// doi: 10.1124/pr.55.1.2.
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