Document Type : Original Research


1 Department of Anatomical Sciences, Jahrom University of Medical Sciences, Jahrom, Iran

2 Student Research Committee, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran

3 Departments of Microbiology, Advanced Medical Sciences and Technology, Jahrom University of Medical Sciences, Jahrom, Iran

4 Department of Pharmacology, Advanced Medical Sciences and Technology, Jahrom University of Medical Sciences, Jahrom, Iran

5 Oral and Dental Disease Research Center, Department of Oral & Maxillofacial Medicine, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran

6 Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran


Background & Objective: The spread and development of drug-resistant bacterial strains has prompted the hunt for novel antibacterial polypeptides undergoing conformational changes to confer rapid bactericidal effects. The aim of this study was to evaluate the effect of novel BMAP27-Melittin conjugated peptide- nanoparticle (NP) against Streptococcus mutans as the primary pathogen from subgingival plaques.
Methods: Sixty subgingival plaque samples were collected, and 39 S. mutans isolates were identified. The BMAP27-Melittin conjugated peptide was purchased from GenScript Company, USA. Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), Biofilm Inhibitory Concentration (BIC), and Biofilm Eradication Concentration (BEC) of BMAP27-Melittin-NP were calculated using the microtiter method.
Results: Thirty-nine infected subjects were reported, including 24 males and 15 females (P=0.299). MIC, MBC, BIC, and BEC of BMAP27-Melittin–NP against S. mutans were 1.8, 2.9, 2.1, and 3.8μg/mL, respectively. The mean MBC, BEC, and BIC values were significantly lower among clinical isolates than S. mutans ATCC 35688 standard strain (P=0.032, 0.001, and 0.001, respectively).
Conclusion: BMAP27-Melittin-NP demonstrated significant antibacterial and anti-biofilm effects against clinical isolates of S. mutans which can be considered a promising compound to prevent or treat dental caries and eradicate the oral infections.


Main Subjects

  1. Pitts NB, Zero DT, Marsh PD, Ekstrand K, Weintraub JA, Ramos-Gomez F, et al. Dental caries. Nat Rev Dis Primers. 2017;3(1):17030. [DOI:10.1038/nrdp.2017.30] [PMID]
  2. Bowen WH, Burne RA, Wu H, Koo H. Oral Biofilms: Pathogens, Matrix, and Polymicrobial Interactions in Microenvironments. Trends Microbiol. 2018;26(3):229-42. [PMID] [PMCID] [DOI:10.1016/j.tim.2017.09.008]
  3. Høiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O. Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents. 2010;35(4):322-32. [PMID] [DOI:10.1016/j.ijantimicag.2009.12.011]
  4. Banas JA. Virulence properties of Streptococcus mutans. Front Biosci. 2004;9(10):1267-77. [DOI:10.2741/1305] [PMID]
  5. Senadheera D, Cvitkovitch DG. Quorum sensing and biofilm formation by Streptococcus mutans. Adv Exp Med Biol. 2008;631:178-88. [DOI:10.1007/978-0-387-78885-2_12] [PMID]
  6. Rozen R, Bachrach G, Bronshteyn M, Gedalia I, Steinberg D. The role of fructans on dental biofilm formation by Streptococcus sobrinus, Streptococcus mutans, Streptococcus gordonii and Actinomyces viscosus. FEMS Microbiol Lett. 2001;195(2):205-10. [DOI:10.1111/j.1574-6968.2001.tb10522.x] [PMID]
  7. Huang R, Li M, Gregory RL. Nicotine promotes Streptococcus mutans extracellular polysaccharide synthesis, cell aggregation and overall lactate dehydrogenase activity. Arch Oral Biol. 2015;60(8):1083-90. [DOI:10.1016/j.archoralbio.2015.04.011] [PMID]
  8. Nakano K, Nomura R, Ooshima T. Streptococcus mutans and cardiovascular diseases. Jpn Dent Sci Rev. 2008;44(1):29-37. [DOI:10.1016/j.jdsr.2007.09.001]
  9. Xiao Y, Reis LA, Feric N, Knee EJ, Gu J, Cao S, et al. Diabetic wound regeneration using peptide-modified hydrogels to target re-epithelialization. Proc Natl Acad Sci. 2016;113(40):E5792-E801. [DOI:10.1073/pnas.1612277113] [PMID] [PMCID]
  10. Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. P T. 2015;40(4):277-83.
  11. Makowski M, Silva IC, Pais do Amaral C, Goncalves S, Santos NC. Advances in Lipid and Metal Nanoparticles for Antimicrobial Peptide Delivery. Pharmaceutics. 2019;11(11):588. [DOI:10.3390/pharmaceutics11110588] [PMID] [PMCID]
  12. Cabrele C, Martinek TA, Reiser O, Berlicki L. Peptides containing beta-amino acid patterns: challenges and successes in medicinal chemistry. J Med Chem. 2014;57(23):9718-39. [DOI:10.1021/jm5010896] [PMID]
  13. Wiesner J, Vilcinskas A. Antimicrobial peptides: the ancient arm of the human immune system. Virulence. 2010;1(5):440-64. [DOI:10.4161/viru.1.5.12983] [PMID]
  14. Patrulea V, Borchard G, Jordan O. An update on antimicrobial peptides (AMPs) and their delivery strategies for wound infections. Pharmaceutics. 2020;12(9):840. [PMID] [PMCID] [DOI:10.3390/pharmaceutics12090840]
  15. Lei J, Sun L, Huang S, Zhu C, Li P, He J, et al. The antimicrobial peptides and their potential clinical applications. Am J Transl Res. 2019;11(7):3919.
  16. Marr AK, Gooderham WJ, Hancock RE. Antibacterial peptides for therapeutic use: obstacles and realistic outlook. Current Opin Pharmacol. 2006;6(5):468-72. [DOI:10.1016/j.coph.2006.04.006] [PMID]
  17. Almaaytah A, Qaoud MT, Abualhaijaa A, Al-Balas Q, Alzoubi KH. Hybridization and antibiotic synergism as a tool for reducing the cytotoxicity of antimicrobial peptides. Infect Drug Resist. 2018;11:835. [DOI:10.2147/IDR.S166236] [PMID] [PMCID]
  18. Park Y, Lee DG, Hahm KS. HP (2-9)‐magainin 2 (1-12), a synthetic hybrid peptide, exerts its antifungal effect on Candida albicans by damaging the plasma membrane. J Pept Sci. 2004;10(4):204-9. [DOI:10.1002/psc.489] [PMID]
  19. Yang S, Lee CW, Kim HJ, Jung HH, Kim JI, Shin SY, et al. Structural analysis and mode of action of BMAP-27, a cathelicidin-derived antimicrobial peptide. Peptides. 2019;118:170106. [DOI:10.1016/j.peptides.2019.170106] [PMID]
  20. Azmi S, Verma NK, Tripathi JK, Srivastava S, Verma DP, Ghosh JK. Introduction of cell‐selectivity in bovine cathelicidin BMAP‐28 by exchanging heptadic isoleucine with the adjacent proline at a non‐heptadic position. Pept Sci. 2021;113(3):e24207. [DOI:10.1002/pep2.24207]
  21. Raghuraman H, Chattopadhyay A. Melittin: a membrane-active peptide with diverse functions. Biosci Rep. 2007;27(4-5):189-223. [DOI:10.1007/s10540-006-9030-z] [PMID]
  22. Tosteson M. Holmes SJ, Razin M, and Tosteson DC. J Membr Biol. 1985;87:35-44. [DOI:10.1007/BF01870697] [PMID]
  23. Fennell JF, Shipman WH, Cole LJ. Antibacterial action of melittin, a polypeptide from bee venom. Proc Soc Exp Biol Med. 1968;127(3):707-10. [DOI:10.3181/00379727-127-32779] [PMID]
  24. Almaaytah A, Tarazi S, Al-Fandi M, Abuilhaija A, Al-shar'i N, Al-Balas Q, et al. The design and functional characterization of the antimicrobial and antibiofilm activities of BMAP27-melittin, a rationally designed hybrid peptide. Int J Pept Res Ther. 2015;21(2):165-77. [DOI:10.1007/s10989-014-9444-6]
  25. Liu L, Xu K, Wang H, Jeremy Tan P, Fan W, Venkatraman SS, et al. Self-assembled cationic peptide nanoparticles as an efficient antimicrobial agent. Nat Nanotechnol. 2009;4(7):457-63. [DOI:10.1038/nnano.2009.153] [PMID]
  26. Jeong W-j, Bu J, Kubiatowicz LJ, Chen SS, Kim Y, Hong S. Peptide-nanoparticle conjugates: a next generation of diagnostic and therapeutic platforms? Nano Converg. 2018;5(1):1-18. [DOI:10.1186/s40580-018-0170-1] [PMID] [PMCID]
  27. Young DA. Development of a Hydrogel Nanoparticle System for Sustained Delivery of Anigogenic Factors for Therapeutic Neovascularization: Illinois Institute of Technology; 2018.
  28. Bělinová T. Interactions of cells with nanoparticles for bio-medical applications. 2020.
  29. Gomes BP, Pinheiro ET, Gade-Neto CR, Sousa EL, Ferraz CC, Zaia AA, et al. Microbiological examination of infected dental root canals. Oral Microbiol Immunol. 2004;19(2):71-6. [DOI:10.1046/j.0902-0055.2003.00116.x] [PMID]
  30. Najafi S, Mardani M, Motamedifar M, Nazarinia M A, Hadadi M. Salivary Streptococcus mutans and Lactobacilli Levels as Indicators of Dental Caries Development in Iranian Patients with Systemic Sclerosis. Iran J Med Microbiol. 2022; 16 (4) :350-356. [DOI: 30699/ijmm.16.4.350]
  31. Okada M, Soda Y, Hayashi F, Doi T, Suzuki J, Miura K, et al. Longitudinal study of dental caries incidence associated with Streptococcus mutans and Streptococcus sobrinus in pre-school children. J Med Microbiol. 2005;54(Pt 7):661-5. [DOI:10.1099/jmm.0.46069-0] [PMID]
  32. Krzyściak W, Jurczak A, Kościelniak D, Bystrowska B, Skalniak A. The virulence of Streptococcus mutans and the ability to form biofilms. Euro J Clin Microbiol Infect Dis. 2014;33(4):499-515. [DOI:10.1007/s10096-013-1993-7] [PMID] [PMCID]
  33. Wang H-Y, Cheng J-W, Yu H-Y, Lin L, Chih Y-H, Pan Y-P. Efficacy of a novel antimicrobial peptide against periodontal pathogens in both planktonic and polymicrobial biofilm states. Acta Biomater. 2015;25:150-61. [DOI:10.1016/j.actbio.2015.07.031] [PMID]
  34. Jorge P, Lourenco A, Pereira MO. New trends in peptide-based anti-biofilm strategies: a review of recent achievements and bioinformatic approaches. Biofouling. 2012;28(10):1033-61. [DOI:10.1080/08927014.2012.728210] [PMID]
  35. Wang Z, de la Fuente-Nunez C, Shen Y, Haapasalo M, Hancock RE. Treatment of Oral Multispecies Biofilms by an Anti-Biofilm Peptide. PloS One. 2015;10(7):e0132512. [PMID] [PMCID] [DOI:10.1371/journal.pone.0132512]
  36. Khurshid Z, Naseem M, Sheikh Z, Najeeb S, Shahab S, Zafar MS. Oral antimicrobial peptides: Types and role in the oral cavity. Saudi Pharm J. 2016;24(5):515-24. [PMID] [PMCID] [DOI:10.1016/j.jsps.2015.02.015]
  37. Lopes BS, Hanafiah A, Nachimuthu R, Muthupandian S, Md Nesran ZN, Patil S. The Role of Antimicrobial Peptides as Antimicrobial and Antibiofilm Agents in Tackling the Silent Pandemic of Antimicrobial Resistance. Molecules. 2022;27(9):2995. [PMID] [PMCID] [DOI:10.3390/molecules27092995]
  38. Leiva-Sabadini C, Alvarez S, Barrera NP, Schuh C, Aguayo S. Antibacterial Effect of Honey-Derived Exosomes Containing Antimicrobial Peptides Against Oral Streptococci. Int J Nanomedicine. 2021;16:4891-900. [DOI:10.2147/IJN.S315040] [PMID] [PMCID]
  39. Ridyard KE, Overhage J. The potential of human peptide LL-37 as an antimicrobial and anti-biofilm agent. Antibiotics. 2021;10(6):650. [PMID] [PMCID] [DOI:10.3390/antibiotics10060650]