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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

The Antimicrobial Effect Against Multi-drug Resistant Bacteria of the SK4 Peptide: A Novel Hybrid Peptide of Cecropin-A and BMAP-27

Author(s): Majed M. Masadeh*, Salam Abu Laila, Razan Haddad, Karem Alzoubi, Ahmad Abu Alhaijaa and Nasr Alrabadi

Volume 24, Issue 8, 2023

Published on: 21 November, 2022

Page: [1070 - 1078] Pages: 9

DOI: 10.2174/1566524023666221031144028

Price: $65

Abstract

Background: Antibiotic-resistant is considered one of the critical health challenges in the management of infectious diseases. Resistant bacterial strains to different antibacterial agents have been spread worldwide. Anti-microbial peptides (AMPs), also called host defense peptides, have a broad spectrum of activity and targeting even to multi-drug resistant (MDR) bacteria, therefore, they have been extensively studied and developed as novel therapeutic antibacterial agents.

Objectives: The study aims to design a novel SK4 hybrid peptide with improved characteristics compared with the BMAP-27 and Cecropin-A natural parents’ peptides.

Methods: The bioinformatic analysis of the SK4 peptide compared with the parents BMAP-27 and Cecropin-A peptides was conducted and fully characterized using specialized software. The antimicrobial and antibiofilm activity of SK4 was tested, followed by a synergistic study with five conventional antibiotics (Levofloxacin, Rifampicin, Chloramphenicol, Doxycycline, and Ampicillin). Finally, the cytotoxicity against horse erythrocytes and mammalian cells was assessed.

Results: The SK4 peptide demonstrated broad-spectrum antimicrobial activity against both grampositive and gram-negative bacteria. The peptide also did not show any hemolytic activity even when used at concentrations ten folds higher than its MICs value. The SK4 peptide also showed a synergistic mode of action when combined with antibiotics, which resulted in a significant decrease in MIC values for both the peptide and the antibiotics.

Conclusion: The SK4 peptide showed better activity, selectivity, and safety profile than the parent peptides, making it a novel potential treatment for MDR bacterial infections.

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[1]
Acar, J.F. Consequences of bacterial resistance to antibiotics in medical practice. Clin. Infect. Dis., 1997, 24(S1), S17-S18.
[http://dx.doi.org/10.1093/clinids/24.Supplement_1.S17] [PMID: 8994777]
[2]
Cornaglia, G. Fighting infections due to multidrug-resistant gram-positive pathogens. Clin. Microbiol. Infect., 2009, 15(3), 209-211.
[http://dx.doi.org/10.1111/j.1469-0691.2009.02737.x] [PMID: 19335367]
[3]
Tan, T.T. “Future” threat of gram-negative resistance in Singapore. Ann. Acad. Med. Singap., 2008, 37(10), 884-890.
[PMID: 19037523]
[4]
Bartlett, J.G.; Gilbert, D.N.; Spellberg, B. Seven ways to preserve the miracle of antibiotics. Clin. Infect. Dis., 2013, 56(10), 1445-1450.
[http://dx.doi.org/10.1093/cid/cit070] [PMID: 23403172]
[5]
Piddock, L.J.V. The crisis of no new antibiotics—what is the way forward? Lancet Infect. Dis., 2012, 12(3), 249-253.
[http://dx.doi.org/10.1016/S1473-3099(11)70316-4] [PMID: 22101066]
[6]
Spellberg, B.; Guidos, R.; Gilbert, D.; Bradley, J.; Boucher, H.W.; Scheld, W.M.; Bartlett, J.G.; Edwards, J., Jr The epidemic of antibiotic-resistant infections: A call to action for the medical community from the infectious diseases society of America. Clin. Infect. Dis., 2008, 46(2), 155-164.
[http://dx.doi.org/10.1086/524891] [PMID: 18171244]
[7]
Spellberg, B.; Bartlett, J.G.; Gilbert, D.N. The future of antibiotics and resistance. N. Engl. J. Med., 2013, 368(4), 299-302.
[http://dx.doi.org/10.1056/NEJMp1215093] [PMID: 23343059]
[8]
Iwasaki, A.; Medzhitov, R. Control of adaptive immunity by the innate immune system. Nat. Immunol., 2015, 16(4), 343-353.
[http://dx.doi.org/10.1038/ni.3123] [PMID: 25789684]
[9]
Nguyen, L.T.; Haney, E.F.; Vogel, H.J. The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol., 2011, 29(9), 464-472.
[http://dx.doi.org/10.1016/j.tibtech.2011.05.001] [PMID: 21680034]
[10]
Reddy, K.V.R.; Yedery, R.D.; Aranha, C. Antimicrobial peptides: Premises and promises. Int. J. Antimicrob. Agents, 2004, 24(6), 536-547.
[http://dx.doi.org/10.1016/j.ijantimicag.2004.09.005] [PMID: 15555874]
[11]
Zasloff, M. Antimicrobial peptides: Do they have a future as therapeutics? PLoS Pathog., 2010, 6(10), e1001067.
[12]
Mookherjee, N.; Anderson, M.A.; Haagsman, H.P.; Davidson, D.J. Antimicrobial host defence peptides: Functions and clinical potential. Nat. Rev. Drug Discov., 2020, 19(5), 311-332.
[http://dx.doi.org/10.1038/s41573-019-0058-8] [PMID: 32107480]
[13]
Dathe, M.; Wieprecht, T. Structural features of helical antimicrobial peptides: Their potential to modulate activity on model membranes and biological cells. Biochim. Biophys. Acta Biomembr., 1999, 1462(1-2), 71-87.
[http://dx.doi.org/10.1016/S0005-2736(99)00201-1] [PMID: 10590303]
[14]
Yeaman, M.R.; Yount, N.Y. Mechanisms of antimicrobial peptide action and resistance. Pharmacol. Rev., 2003, 55(1), 27-55.
[http://dx.doi.org/10.1124/pr.55.1.2] [PMID: 12615953]
[15]
Marr, A.; Gooderham, W.; Hancock, R. Antibacterial peptides for therapeutic use: Obstacles and realistic outlook. Curr. Opin. Pharmacol., 2006, 6(5), 468-472.
[http://dx.doi.org/10.1016/j.coph.2006.04.006] [PMID: 16890021]
[16]
Almaaytah, A.; Qaoud, M.T.; Abualhaijaa, A.; Al-Balas, Q.; Alzoubi, K.H. Hybridization and antibiotic synergism as a tool for reducing the cytotoxicity of antimicrobial peptides. Infect. Drug Resist., 2018, 11, 835-847.
[http://dx.doi.org/10.2147/IDR.S166236] [PMID: 29910626]
[17]
Oren, Z.; Shai, Y. Mode of action of linear amphipathic α-helical antimicrobial peptides. Biopolymers, 1998, 47(6), 451-463.
[http://dx.doi.org/10.1002/(SICI)1097-0282(1998)47:6<451::AIDBIP4>3.0.CO;2-F] [PMID: 10333737]
[18]
Yang, Y.; Wu, D.; Wang, C.; Shan, A.; Bi, C.; Li, Y.; Gan, W. Hybridization with insect cecropin A (1–8) improve the stability and selectivity of naturally occurring peptides. Int. J. Mol. Sci., 2020, 21(4), 1470.
[http://dx.doi.org/10.3390/ijms21041470] [PMID: 32098142]
[19]
Malanovic, N.; Leber, R.; Schmuck, M.; Kriechbaum, M.; Cordfunke, R.A.; Drijfhout, J.W.; de Breij, A.; Nibbering, P.H.; Kolb, D.; Lohner, K. Phospholipid-driven differences determine the action of the synthetic antimicrobial peptide OP-145 on gram-positive bacterial and mammalian membrane model systems. Biochim. Biophys. Acta Biomembr., 2015, 1848(10), 2437-2447.
[http://dx.doi.org/10.1016/j.bbamem.2015.07.010] [PMID: 26210299]
[20]
Pompilio, A.; Scocchi, M.; Pomponio, S.; Guida, F.; Di Primio, A.; Fiscarelli, E.; Gennaro, R.; Di Bonaventura, G. Antibacterial and anti-biofilm effects of cathelicidin peptides against pathogens isolated from cystic fibrosis patients. Peptides, 2011, 32(9), 1807-1814.
[http://dx.doi.org/10.1016/j.peptides.2011.08.002] [PMID: 21849157]
[21]
Bussmann, R.W.; Malca-García, G.; Glenn, A.; Sharon, D.; Chait, G.; Díaz, D.; Pourmand, K.; Jonat, B.; Somogy, S.; Guardado, G.; Aguirre, C.; Chan, R.; Meyer, K.; Kuhlman, A.; Townesmith, A.; Effio-Carbajal, J.; Frías-Fernandez, F.; Benito, M. Minimum inhibitory concentrations of medicinal plants used in Northern Peru as antibacterial remedies. J. Ethnopharmacol., 2010, 132(1), 101-108.
[http://dx.doi.org/10.1016/j.jep.2010.07.048] [PMID: 20678568]
[22]
Komatsuzawa, H.; Ohta, K.; Sugai, M.; Fujiwara, T.; Glanzmann, P.; Berger-Bachi, B.; Suginaka, H. Tn551-mediated insertional inactivation of the fmtB gene encoding a cell wall-associated protein abolishes methicillin resistance in Staphylococcus aureus. J. Antimicrob. Chemother., 2000, 45(4), 421-431.
[http://dx.doi.org/10.1093/jac/45.4.421] [PMID: 10896508]
[23]
Sueke, H.; Kaye, S.B.; Neal, T.; Hall, A.; Tuft, S.; Parry, C.M. An in vitro investigation of synergy or antagonism between antimicrobial combinations against isolates from bacterial keratitis. Invest. Ophthalmol. Vis. Sci., 2010, 51(8), 4151-4155.
[http://dx.doi.org/10.1167/iovs.09-4839] [PMID: 20335613]
[24]
Zhang, L.; Rozek, A.; Hancock, R.E.W. Interaction of cationic antimicrobial peptides with model membranes. J. Biol. Chem., 2001, 276(38), 35714-35722.
[http://dx.doi.org/10.1074/jbc.M104925200] [PMID: 11473117]
[25]
Hancock, R.E. Antibacterial peptides and the outer membranes of gram-negative bacillixs. J. Med. Microbiol., 1997, 46(1), 1-3.
[http://dx.doi.org/10.1099/00222615-46-1-1] [PMID: 9003734]
[26]
Risso, A.; Zanetti, M.; Gennaro, R. Cytotoxicity and apoptosis mediated by two peptides of innate immunity. Cell. Immunol., 1998, 189(2), 107-115.
[http://dx.doi.org/10.1006/cimm.1998.1358] [PMID: 9790724]
[27]
Glukhov, E.; Stark, M.; Burrows, L.L.; Deber, C.M. Basis for selectivity of cationic antimicrobial peptides for bacterial versus mammalian membranes. J. Biol. Chem., 2005, 280(40), 33960-33967.
[http://dx.doi.org/10.1074/jbc.M507042200] [PMID: 16043484]

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