Suppressive effects of gecko cathelicidin on biofilm formation and cariogenic virulence factors of Streptococcus mutans
Suppressive effects of gecko cathelicidin on biofilm formation and cariogenic virulence factors of Streptococcus mutans
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壁虎抗菌素对变形链球菌生物膜形成和致龋毒力因子的抑制作用
DOI：
10.1016/j.archoralbio.2021.105205
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发表时间：
2021-07-05
影响因子：
3
通讯作者：
Wang, Guannan
中科院分区：
文献类型：
--
作者：
Cai, Shasha;Meng, Kai;Wang, Guannan
目的：研究壁虎毒素GJ-CATH2对变形链球菌生物被膜形成和致龋性毒力因子的影响，并初步探讨其作用机制。设计：采用最低抑菌浓度和杀菌动力学方法评价GJ-CATH2的抑菌作用。采用结晶紫染色和扫描电子显微镜观察GJ-CATH2对变形链球菌生物被膜形成的影响。研究了GJ-CATH2对变形链球菌胞外多糖(EPS)合成、细菌聚集、产酸性和耐酸性的影响。通过实时定量聚合酶链式反应获得相关基因的表达谱。结果：GJ-CATH2对变形链球菌有较强的杀菌和抗生物被膜作用。扫描电子显微镜证实，GJ-CATH2处理组变形链球菌生物膜内致密结构减少。GJ-CATH2对变形链球菌的EPS合成、细胞聚集、产酸有明显的抑制作用，但对其耐酸性无明显影响。此外，GJ-CATH2显著抑制了与生物膜形成(GTFB/C/D、gbpB/D)、群体感应系统(LuxS和COMD/E)和产酸性(LDH)相关的基因的表达。GJ-CATH2在人类唾液中也显示出有利的抵抗力，对哺乳动物细胞的毒性可以忽略不计。结论：GJ-CATH2通过靶向细菌黏附和生物膜成熟阶段抑制变形链球菌生物被膜的形成。GJ-CATH2显著抑制变形链球菌毒力因子的产生，导致EPS合成减少，降低细菌的产酸能力。提示GJ-CATH2可能是一种具有临床应用前景的防龋剂。
Objective: The aims of this study were to investigate the effectivity of gecko cathelicidin Gj-CATH2 on biofilm formation and cariogenic virulence factors of S. mutans, and preliminary explore its function mechanisms. Design: Minimum inhibitory concentration and bacterial killing kinetics assays were performed to assess the antimicrobial effect of Gj-CATH2.The influence of Gj-CATH2 on S. mutans biofilm formation was determined by crystal violet staining method and observed by SEM. The effects of Gj-CATH2 on exopolysaccharides (EPS) synthesis, bacterial aggregation, acidogenicity and aciduricity of S. mutans were also investigated. Quantitative real-time PCR was conducted to acquire the expression profile of related genes. Results: Gj-CATH2 showed strong bactericidal and anti-biofilm effects on S. mutans. SEM confirmed the reduction of the dense structure in S. mutans biofilm in Gj-CATH2-treated groups. Gj-CATH2 significantly inhibited EPS synthesis, cell aggregation, acid production of S. mutans, but showed no influence on its acid proof. Furthermore, the expression of genes related to biofilm formation (gtfB/C/D, gbpB/D), quorum sensing system (luxS and comD/ E) and acidogenicity (ldh) was significantly suppressed by Gj-CATH2. Gj-CATH2 also displayed advantageous resistance in human saliva and exhibited negligible toxicity against mammalian cells. Conclusions: Gj-CATH2 inhibited S. mutans biofilm formation by targeting the bacterial adhesion and the biofilm maturation stages. Gj-CATH2 significantly suppressed virulence factors production of S. mutans, resulting in decreased EPS synthesis and reduced acidogenicity of bacteria. These findings suggest Gj-CATH2 might be a promising agent for clinical application in prevention of dental caries.