人工合成抗菌肽在龋病防治中的研究进展

doi:10.13591/j.cnki.kqyx.2022.12.015

摘要/Abstract

摘要： 抗菌肽(antimicrobial peptides, AMPs)具有很强的抗菌作用,由于其独特的杀菌机制,被认为是传统抗生素的潜在替代品。相对于天然抗菌肽,人工合成抗菌肽具有更好的抗菌活性和稳定性,可以从抑制主要致龋菌、减少牙菌斑生物膜形成和促进再矿化等方面对龋病进行预防和治疗。该文将对用于龋病防治的人工合成抗菌肽及其作用机制进行综述,为进一步深入研究人工合成抗菌肽在龋病防治中的应用提供参考依据。

关键词: 人工合成抗菌肽, 龋病, 变异链球菌, 生物膜, 再矿化

Abstract: Antimicrobial peptides have strong antibacterial effects and are considered as a potential alternative to traditional antibiotics due to their unique bactericidal mechanism. Compared with natural antimicrobial peptides, synthetic antimicrobial peptides have better antibacterial activity and stability, and can be used for dental caries prevention and treatment in terms of inhibiting major cariogenic bacteria, reducing the formation of dental plaque biofilm, and promoting remineralization. This paper will review these synthetic antimicrobial peptides and their mechanisms, and provide a reference for further study on synthetic antimicrobial peptides in caries prevention and treatment.

Key words: synthetic antimicrobial peptide, dental caries, Streptococcus mutans, biofilm, tooth remineralization

中图分类号:

R781.1

袁文锦, 韩佳岐, 杨婕, 董宁, 姜秋. 人工合成抗菌肽在龋病防治中的研究进展[J]. 口腔医学, 2022, 42(12): 1129-1133.

YUAN Wenjin, HAN Jiaqi, YANG Jie, DONG Ning, JIANG Qiu. Research progress of synthetic antimicrobial peptides in prevention and treatment of dental caries[J]. Stomatology, 2022, 42(12): 1129-1133.

参考文献

[1] Dye BA. The global burden of oral disease: Research and public health significance[J]. J Dent Res, 2017, 96(4):361-363.
[2] Cieplik F, Jakubovics NS, Buchalla W, et al. Resistance toward chlorhexidine in oral bacteria is there cause for concern?[J]. Front Microbiol, 2019, 10: 587.
[3] Zhang JY, Chen CX, Chen JX, et al. Dual mode of anti-biofilm action of G3 against Streptococcus mutans[J]. ACS Appl Mater Interfaces, 2020, 12(25):27866-27875.
[4] Niu JY, Yin IX, Mei ML, et al. The multifaceted roles of antimicrobial peptides in oral diseases[J]. Mol Oral Microbiol, 2021, 36(3):159-171.
[5] Shao CX, Zhu YJ, Lai ZH, et al. Antimicrobial peptides with protease stability: Progress and perspective[J]. Future Med Chem, 2019, 11(16):2047-2050.
[6] Pitts NB, Zero DT, Marsh PD, et al. Dental caries[J]. Nat Rev Dis Primers, 2017, 3: 17030.
[7] Liang JH, Liang DS, Liang YE, et al. Effects of a derivative of reutericin 6 and gassericin A on the biofilm of Streptococcus mutans in vitro and caries prevention in vivo[J]. Odontology, 2021, 109(1):53-66.
[8] Liang DS, Li HY, Xu XH, et al. Rational design of peptides with enhanced antimicrobial and anti-biofilm activities against cariogenic bacterium Streptococcus mutans[J]. Chem Biol Drug Des, 2019, 94(4):1768-1781.
[9] 梁东生, 李焕影, 许晓虎, 等. 抗变异链球菌多肽的设计、筛选及抗菌效果评价[J]. 南方医科大学学报, 2019, 39(7):823-829.
[10] 何佳宁, 梁东生, 梁悦娥, 等. 新型抗菌肽KR-1的设计、筛选及抗菌活性评价[J]. 南方医科大学学报, 2021, 41(6):923-930.
[11] Wei HQ, Xie ZP, Tan XC, et al. Temporin-like peptides show antimicrobial and anti-biofilm activities against Streptococcus mutans with reduced hemolysis[J]. Molecules, 2020, 25(23):5724.
[12] Hawrani A, Howe RA, Walsh TR, et al. Origin of low mammalian cell toxicity in a class of highly active antimicrobial amphipathic helical peptides[J]. J Biol Chem, 2008, 283(27):18636-18645.
[13] Cruz J, Ortiz C, Guzmán F, et al. Design and activity of novel lactoferrampin analogues against O157: H7 enterohemorrhagic Escherichia coli[J]. Biopolymers, 2014, 101(4):319-328.
[14] Luo JY, Feng ZN, Jiang WT, et al. Novel lactotransferrin-derived synthetic peptides suppress cariogenic bacteria in vitro and arrest dental caries in vivo:[Novel lactotransferrin-derived anticaries peptides[J]. J Oral Microbiol, 2021, 13(1):1943999.
[15] Chen Z, Yang G, Lu SS, et al. Design and antimicrobial activities of LL-37 derivatives inhibiting the formation of Streptococcus mutans biofilm[J]. Chem Biol Drug Des, 2019, 93(6):1175-1185.
[16] Wang GS. Structures of human host defense cathelicidin LL-37 and its smallest antimicrobial peptide KR-12 in lipid micelles[J]. J Biol Chem, 2008, 283(47):32637-32643.
[17] da Silva BR, Conrado AJS, Pereira AL, et al. Antibacterial activity of a novel antimicrobial peptide[W7]KR12-KAEK derived from KR-12 against Streptococcus mutans planktonic cells and biofilms[J]. Biofouling, 2017, 33(10):835-846.
[18] Kokilakanit P, Koontongkaew S, Roytrakul S, et al. A novel non-cytotoxic synthetic peptide, Pug-1, exhibited an antibiofilm effect on Streptococcus mutans adhesion[J]. Lett Appl Microbiol, 2020, 70(3):151-158.
[19] Zhang LY, Fang ZH, Li QL, et al. A tooth-binding antimicrobial peptide to prevent the formation of dental biofilm[J]. J Mater Sci Mater Med, 2019, 30(4):45.
[20] Eckert R, Qi FX, Yarbrough DK, et al. Adding selectivity to antimicrobial peptides: Rational design of a multidomain peptide against Pseudomonas spp[J]. Antimicrob Agents Chemother, 2006, 50(4):1480-1488.
[21] 侯梦瑶, 孙应明, 营秀, 等. C8gpm11抗菌肽对口内常见致病菌的作用研究[J]. 安徽医科大学学报, 2018, 53(4):580-584.
[22] Jiang WT, Wang YF, Luo JY, et al. Antimicrobial peptide GH12 prevents dental caries by regulating dental plaque microbiota[J]. Appl Environ Microbiol, 2020, 86(14):e00527-e00520.
[23] Tsuzukibashi O, Uchibori S, Kobayashi T, et al. Isolation and identification methods of Rothia species in oral cavities[J]. J Microbiol Methods, 2017, 134: 21-26.
[24] Kashiwada A, Mizuno M, Hashimoto J. pH-Dependent membrane Lysis by using melittin-inspired designed peptides[J]. Org Biomol Chem, 2016, 14(26):6281-6288.
[25] Jiang WT, Luo JY, Wang YF, et al. The pH-responsive property of antimicrobial peptide GH12 enhances its anticaries effects at acidic pH[J]. Caries Res, 2021, 55(1):21-31.
[26] Ajdic D, Chen Z. A novel phosphotransferase system of Streptococcus mutans is responsible for transport of carbohydrates with α-1, 3 linkage[J]. Mol Oral Microbiol, 2013, 28(2):114-128.
[27] Xiang SW, Shao J, He J, et al. A membrane-targeted peptide inhibiting PtxA of phosphotransferase system blocks Streptococcus mutans[J]. Caries Res, 2019, 53(2):176-193.
[28] Niu JY, Yin IX, Wu WKK, et al. A novel dual-action antimicrobial peptide for caries management[J]. J Dent, 2021, 111:103729.
[29] Zhang MJ, Wei W, Sun YM, et al. Pleurocidin congeners demonstrate activity against Streptococcus and low toxicity on gingival fibroblasts[J]. Arch Oral Biol, 2016, 70:79-87.
[30] Wang YF, Wang XQ, Jiang WT, et al. Antimicrobial peptide GH12 suppresses cariogenic virulence factors of Streptococcus mutans[J]. J Oral Microbiol, 2018, 10(1):1442089.
[31] Culp DJ, Hull W, Bremgartner MJ, et al. In vivo colonization with candidate oral probiotics attenuates Streptococcus mutans colonization and virulence[J]. Appl Environ Microbiol, 2021, 87(4):e02490-20.
[32] Colombo APV, Tanner ACR. The role of bacterial biofilms in dental caries and periodontal and peri-implant diseases: A historical perspective[J]. J Dent Res, 2019, 98(4):373-385.
[33] Yu OY, Zhao IS, Mei ML, et al. Dental biofilm and laboratory microbial culture models for cariology research[J]. Dent J (Basel), 2017, 5(2):21.
[34] Rabin N, Zheng Y, Opoku-Temeng C, et al. Biofilm formation mechanisms and targets for developing antibiofilm agents[J]. Future Med Chem, 2015, 7(4):493-512.
[35] Batoni G, Maisetta G, Esin S. Antimicrobial peptides and their interaction with biofilms of medically relevant bacteria[J]. Biochim Biophys Acta, 2016, 1858(5):1044-1060.
[36] Wang YF, Zeng YH, Wang YJ, et al. Antimicrobial peptide GH12 targets Streptococcus mutans to arrest caries development in rats[J]. J Oral Microbiol, 2019, 11(1):1549921.
[37] Jiang WT, Wang YF, Luo JY, et al. Effects of antimicrobial peptide GH12 on the cariogenic properties and composition of a cariogenic multi species biofilm[J]. Appl Environ Microbiol, 2018, 84(24):e01423-e01418.
[38] 李欣蔚, 王雨霏, 姜文韬, 等. 抗菌肽GH12对龋相关三菌种生物膜形貌及菌种构成的影响[J]. 华西口腔医学杂志, 2021, 39(2):188-194.
[39] Kim K, An JS, Lim BS, et al. Effect of bisphenol A glycol methacrylate on virulent properties of Streptococcus mutans UA159[J]. Caries Res, 2019, 53(1):84-95.
[40] Liao SM, Klein MI, Heim KP, et al. Streptococcus mutans extracellular DNA is upregulated during growth in biofilms, actively released via membrane vesicles, and influenced by components of the protein secretion machinery[J]. J Bacteriol, 2014, 196(13):2355-2366.
[41] Xiao J, Klein MI, Falsetta ML, et al. The exopolysaccharide matrix modulates the interaction between 3D architecture and virulence of a mixed-species oral biofilm[J]. PLoS Pathog, 2012, 8(4):e1002623.
[42] Niu JY, Yin IX, Wu WKK, et al. Remineralising dentine caries using an artificial antimicrobial peptide: An in vitro study[J]. J Dent, 2021, 111: 103736.
[43] Chen XY, Zaro JL, Shen WC. Fusion protein linkers: Property, design and functionality[J]. Adv Drug Deliv Rev, 2013, 65(10):1357-1369.
[44] Zhou L, Wong HM, Zhang YY, et al. Constructing an antibiofouling and mineralizing bioactive tooth surface to protect against decay and promote self-healing[J]. ACS Appl Mater Interfaces, 2020, 12(2):3021-3031.
[45] Zhou L, Li QL, Wong HM. A novel strategy for caries management: Constructing an antibiofouling and mineralizing dual-bioactive tooth surface[J]. ACS Appl Mater Interfaces, 2021, 13(26):31140-31152.
[46] Krzyściak W, Jurczak A, Piatkowski J, et al. Effect of histatin-5 and lysozyme on the ability of Streptococcus mutans to form biofilms in in vitro conditions[J]. Postepy Hig Med Dosw (Online), 2015, 69: 1056-1066.
[47] Huo LJ, Zhang K, Ling JQ, et al. Antimicrobial and DNA-binding activities of the peptide fragments of human lactoferrin and histatin 5 against Streptococcus mutans[J]. Arch Oral Biol, 2011, 56(9):869-876.
[48] Malanovic N, Lohner K. Antimicrobial peptides targeting gram-positive bacteria[J]. Pharmaceuticals (Basel), 2016, 9(3):59.
[49] Prajatelistia E, Ju SW, Sanandiya ND, et al. Tunicate-inspired Gallic acid/metal ion complex for instant and efficient treatment of dentin hypersensitivity[J]. Adv Healthc Mater, 2016, 5(8):919-927.
[50] Niu JY, Yin IX, Wu WKK, et al. Antimicrobial peptides for the prevention and treatment of dental caries: A concise review[J]. Arch Oral Biol, 2021, 122: 105022.
[51] Li QL, Ning TY, Cao Y, et al. A novel self-assembled oligopeptide amphiphile for biomimetic mineralization of enamel[J]. BMC Biotechnol, 2014, 14: 32.
[52] Wang YF, Fan YY, Zhou ZL, et al. De novo synthetic short antimicrobial peptides against cariogenic bacteria[J]. Arch Oral Biol, 2017, 80: 41-50.
[53] Wang XQ, Wang YF, Wang K, et al. Bifunctional anticaries peptides with antibacterial and remineralizing effects[J]. Oral Dis, 2019, 25(2):488-496.
[54] Valente MT, Moffa EB, Crosara KTB, et al. Acquired enamel pellicle engineered peptides: Effects on hydroxyapatite crystal growth[J]. Sci Rep, 2018, 8(1):3766.
[55] Zhou L, Wong HM, Li QL. Anti-biofouling coatings on the tooth surface and hydroxyapatite[J]. Int J Nanomedicine, 2020, 15: 8963-8982.