变异链球菌噬菌体及裂解酶防治龋病的机制与前景

doi:10.13701/j.cnki.kqyxyj.2026.10.002

摘要/Abstract

摘要： 全球疾病负担数据显示,龋病发病率在全球及中国均呈增长趋势,传统防治策略面临耐药性、生物膜穿透不足及微生态破坏等局限。本文对变异链球菌噬菌体及其裂解酶研究进展进行总结,分析噬菌体的进化特征,裂解酶结构及其在复杂口腔环境中的抗菌机制。研究表明,噬菌体能精准裂解致龋菌并降解生物膜基质,裂解酶通过催化域与结合域协同破坏肽聚糖网络,两者均具备维持口腔微生态平衡的独特优势。但该技术仍存在宿主范围窄,递送效率低及耐药风险等挑战。通过基因编辑、纳米递送系统开发及多模态协同策略,为构建精准安全的龋病靶向防治体系提供新思路。

关键词: 噬菌体疗法, 裂解酶, 龋病防治, 变异链球菌, 生物膜

Abstract: The Global Burden of Disease (GBD) data indicate that the incidence rates of dental caries are exhibiting an increasing trend both globally and in China. Conventional prevention and treatment strategies are facing limitations such as antimicrobial resistance, inadequate biofilm penetration, and disruption of the oral microecological balance. This review synthesizes research progress on Streptococcus mutans phages and their lysins, analyzing phage evolutionary traits, lysin structural modules, and antimicrobial mechanisms in the complex oral environment. Findings demonstrate that phages precisely lyse cariogenic pathogens while degrading biofilm matrices, and phage-encoded lysins synergistically disrupt peptidoglycan networks through catalytic and binding domains-both exhibiting unique advantages in maintaining oral ecological equilibrium. Persistent challenges include limited host spectrum, suboptimal delivery efficiency, and resistance risks. The review proposes targeted solutions encompassing genetic engineering, nanodelivery systems, and multimodal synergistic approaches to establish precision-targeted anti-caries systems with enhanced biosafety.

Key words: phage therapy, lysin, dental caries prevention, Streptococcus mutans, biofilm

王龙玉, 苏少晨. 变异链球菌噬菌体及裂解酶防治龋病的机制与前景[J]. 口腔医学研究, 2026, 42(10): 833-838.

WANG Longyu, SU Shaochen. Anticaries Mechanisms and Prospects of Streptococcus Mutans Bacteriophages and Their Lytic Enzymes[J]. Journal of Oral Science Research, 2026, 42(10): 833-838.

参考文献

[1] Sun R, Xu X, Dong Y, et al. Global and regional trends in prevalence of untreated caries in permanent teeth: Age-period-cohort analysis from 1990 to 2019 and projections until 2049[J]. J Dent, 2024, 147: 105122.
[2] Zhang X, Zhao CN, Zheng H, et al. Burden and predictions of untreated caries in China, 1990-2039: A systematic analysis for the Global Burden of Disease Study 2019[J]. Clin Exp Dent Res, 2025, 11(5): e70211.
[3] Yang Q, Li F, Ye Y, et al. Antimicrobial, remineralization, and infiltration: advanced strategies for interrupting dental caries[J]. Med Rev, 2025, 5(2): 87-116.
[4] Delisle AL, Rostkowski CA. Lytic bacteriophages of Streptococcus mutans[J]. Curr Microbiol, 1993, 27(3): 163-167.
[5] Delisle AL, Guo M, Chalmers NI, et al. Biology and genome sequence of Streptococcus mutans phage M102AD[J]. Appl Environ Microbiol, 2012, 78(7): 2264-2271.
[6] van der Ploeg JR. Genome sequence of Streptococcus mutans bacteriophage M102[J]. FEMS Microbiol Lett, 2007, 275(1): 130-138.
[7] Dalmasso M, De Haas E, Neve H, et al. Isolation of a novel phage with activity against Streptococcus mutans biofilms[J]. PLoS One, 2015, 10(9): e0138651.
[8] Ben-Zaken H, Kraitman R, Coppenhagen-Glazer S, et al. Isolation and characterization of Streptococcus mutans phage as a possible treatment agent for caries[J]. Viruses, 2021, 13(5):825.
[9] Sugai K, Kawada-Matsuo M, Nguyen-Tra Le M , et al. Isolation of Streptococcus mutans temperate bacteriophage with broad killing activity to S. mutans clinical isolates[J]. Iscience, 2023, 26(12):108465.
[10] Jacob F, Fuerst CR. The mechanism of lysis by phage studied with defective lysogenic bacteria[J]. J Gen Microbiol, 1958, 18(2): 518-526.
[11] Diaz E, López R, Garcia JL. Chimeric phage-bacterial enzymes: a clue to the modular evolution of genes[J]. Proc Natl Acad Sci U S A, 1990, 87(20): 8125-8129.
[12] Yang H, Linden SB, Wang J, et al. A chimeolysin with extended-spectrum streptococcal host range found by an induced lysis-based rapid screening method[J]. Sci Rep, 2015, 5: 17257.
[13] Zhao X, Li C, Yang H, et al. Antibacterial activity of a Lysin LysP53 against Streptococcus mutans[J]. J Dent Res, 2023, 102(11): 1231-1240.
[14] Hosseini Hooshiar M, Salari S, Nasiri K, et al. The potential use of bacteriophages as antibacterial agents in dental infection[J]. Virol J, 2024, 21(1): 258.
[15] Gummalla VS, Zhang Y, Liao YT, et al. The role of temperate phages in bacterial pathogenicity[J]. Microorganisms, 2023, 11(3): 541.
[16] Liu H, Hu Z, Li M, et al. Therapeutic potential of bacteriophage endolysins for infections caused by Gram-positive bacteria[J]. J Biomed Sci, 2023, 30(1): 29.
[17] Hu F, Zhang X, Gong Z, et al. Domain interactions in a chimeric dual-domain lysin lead to broad bactericidal activity[J]. J Mol Biol, 2025, 437(21): 169373.
[18] Park JM, Kim JH, Kim G, et al. Rapid antibacterial activity assessment of chimeric lysins[J]. Int J Mol Sci, 2024, 25(4): 2430.
[19] Yi S, Liu Y, Wu Q, et al. Glycosylation of oral bacteria in modulating adhesion and biofilm formation[J]. J Oral Microbiol, 2025, 17(1): 2486650.
[20] Rajabi Z, Soltan Dallal MM, Afradi MR, et al. Comparison of the effect of extracted bacteriocin and lytic bacteriophage on the expression of biofilm associated genes in Streptococcus mutans[J]. Adv Mater Sci Eng, 2022, 2022: 5035280.
[21] Wang H, Liu Y, Bai C, et al. Translating bacteriophage-derived depolymerases into antibacterial therapeutics: Challenges and prospects[J]. Acta Pharm Sin B, 2024, 14(1): 155-169.
[22] Lendel AM, Antonova NP, Grigoriev IV, et al. Biofilm-disrupting effects of phage endolysins LysAm24, LysAp22, LysECD7, and LysSi3: breakdown the matrix[J]. World J Microbiol Biotechnol, 2024, 40(6): 186.
[23] Nakano K, Ooshima T. Serotype classification of Streptococcus mutans and its detection outside the oral cavity[J]. Future microbiol, 2009, 4(7): 891-902.
[24] Yang H, Bi Y, Shang X, et al. Antibiofilm activities of a novel chimeolysin against Streptococcus mutans under physiological and cariogenic conditions[J]. Antimicrob Agents Chemother, 2016, 60(12): 7436-7443.
[25] Xu J, Yang H, Bi Y, et al. Activity of the chimeric lysin ClyR against common gram-positive oral microbes and its anticaries efficacy in rat models[J]. Viruses, 2018, 10(7): 380.
[26] 徐晶晶,陶庭亮,李宇红. 一种噬菌体裂解酶的抗龋作用研究[J].口腔医学研究,2018,34(10): 1052-1056.
[27] Li C, Jiang M, Khan FM, et al. Intrinsic antimicrobial peptide facilitates a new broad-spectrum lysin LysP53 to kill Acinetobacter baumannii in vitro and in a mouse burn infection model[J]. ACS Infect Dis, 2021, 7(12): 3336-3344.
[28] 赵晓苇,陈方圆,危宏平,等. 噬菌体裂解酶LysP53漱口水的制备与评价[J].口腔医学研究,2023,39(6): 553-557.
[29] Wall LA, Wall D. Acquired CRISPR spacers and rhamnose-glucose polysaccharide defects confer resistance to Streptococcus mutans phage ΦAPCM01[J]. Microbiology (Reading), 2025, 171(6): 001575.
[30] Fang Q, Yin X, He Y, et al. Safety and efficacy of phage application in bacterial decolonisation: a systematic review[J]. Lancet Microbe, 2024, 5(5): e489-e499.
[31] Taglialegna A. A master phage cocktail[J]. Nat Rev Microbiol, 2023, 21(7): 411.
[32] El-Din EMRS, Zaki BM, El-Aziz AMA, et al. Bacteriophage-antibiotic synergy enhances therapeutic efficacy against multidrug-resistant Klebsiella pneumoniae infections[J]. J Appl Microbiol, 2025, 136(6):lxaf131.