Department of Stomatology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, People's Republic of China.
Department of Stomatology, Affiliated Zhongshan Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
Odontology. 2021 Jan;109(1):53-66. doi: 10.1007/s10266-020-00529-5. Epub 2020 May 30.
It is known that Streptococcus mutans (S. mutans) is the leading cariogenic pathogen. Recently, an increasing number of antimicrobial peptides (AMPs) have been brought into consideration as anti-caries agents. Here, we designed and synthesized an AMP derived from reutericin 6 and/or gassericin A, named LN-7, and explored its effect on biofilm of S. mutans UA159 in vitro and development of dental caries in vivo. Antibacterial assays showed that LN-7 was more active against S. mutans (3.2 μM) than many peptide-based agents, capable of killing other types of Streptococci in oral cavity. In addition, LN-7 presented fast killing kinetics, with more than 97% S. mutans killed within 5 min. The mechanism of the antimicrobial activity mainly lies on the disruption of bacterial membrane. Effects of LN-7 on the biofilm formation and the viability of preformed biofilm were quantified by crystal violet staining, which showed that LN-7 could effectively inhibit the biofilm accumulation of S. mutans. Moreover, the biofilm of S. mutans treated with LN-7 displayed notable changes in bacterial viability and morphology, observed by confocal laser scanning microscopy and scanning electron microscopy. In addition, topical oral treatment with LN-7 could suppress the development of dental caries in vivo, reducing the occurrence of severe dental lesion in a rodent model. These results reveal a new peptide-based agent as a topical treatment for dental caries, opening the door to clinical studies to explore its potential for caries prevention.
已知变形链球菌（S. mutans）是主要的致龋病原体。最近，越来越多的抗菌肽（AMPs）被认为是抗龋剂。在这里，我们设计并合成了一种源自雷替辛 6 和/或 gassericin A 的 AMP，命名为 LN-7，并探索了其对 S. mutans UA159 体外生物膜和体内龋齿发展的影响。抗菌试验表明，LN-7 对 S. mutans（3.2 μM）的活性高于许多基于肽的试剂，能够杀死口腔中的其他类型链球菌。此外，LN-7 表现出快速杀菌动力学，超过 97%的 S. mutans 在 5 分钟内被杀死。抗菌活性的机制主要在于破坏细菌膜。结晶紫染色定量测定了 LN-7 对生物膜形成和已形成生物膜活力的影响，结果表明 LN-7 能有效抑制 S. mutans 生物膜的积累。此外，通过共聚焦激光扫描显微镜和扫描电子显微镜观察到，用 LN-7 处理的 S. mutans 生物膜的细菌活力和形态发生了明显变化。此外，LN-7 的局部口腔治疗可抑制体内龋齿的发展，减少啮齿动物模型中严重牙损伤的发生。这些结果揭示了一种新的基于肽的试剂作为一种局部治疗龋齿的方法，为探索其在龋齿预防方面的潜力开辟了临床研究的大门。
