State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China.
Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Appl Microbiol Biotechnol. 2020 Apr;104(8):3585-3595. doi: 10.1007/s00253-020-10496-0. Epub 2020 Mar 3.
The prevalence of stomatitis, especially that caused by Candida albicans, has highlighted the need for new antifungal agents. We previously found that a type of quaternary ammonium salts, dimethylaminododecyl methacrylate (DMADDM), incorporated in dental materials inhibited the growth and hyphal development of C. albicans. However, how the quaternary ammonium salts inhibited the fungal pathogens and whether the oral condition, such as salivary pH variation under different diseases, can affect the antimicrobial capacity of quaternary ammonium salts is unknown. This study evaluated the antifungal effects of DMADDM at different pH in vitro and in vivo. A pH-dependent antifungal effect of DMADDM was observed in planktonic and biofilm growth. DMADDM enhanced antifungal activity at alkaline pH. Two pH-regulated genes (PHR1/PHR2) of C. albicans were correlated with the pH-dependent antifungal effects of DMADDM. The PHR1/PHR2 genes and pH values regulated the zeta potential of C. albicans, which then influenced the binding between C. albicans cells and DMADDM. The pH-dependent antifungal activity of DMADDM was then substantiated in a murine oropharyngeal candidiasis model. We directly demonstrated that the antifungal abilities of quaternary ammonium salts relied on the cell zeta potential which affected the binding between fungal cells and quaternary ammonium salts. These findings suggest a new antifungal mechanism of quaternary ammonium under different pH and that DMADDM can be a potential antifungal agent applied in dental materials and stomatitis therapy.Key Points • DMADDM has stronger antifungal activity in alkaline than in acidic pH conditions. • The pH values and pH-regulated genes can affect the zeta potential of fungal cells. • Zeta potential of fungal cells directly affect the binding between DMADDM and cells. Graphical abstract Schematic diagram of the antifungal activities of DMADDM at different pH values.
口腔黏膜炎的流行，特别是白色念珠菌引起的口腔黏膜炎，凸显了对新型抗真菌药物的需求。我们之前发现，一种季铵盐，十二烷基二甲基（甲基）丙烯酰胺（DMADDM），存在于牙科材料中可以抑制白色念珠菌的生长和菌丝发育。然而，季铵盐是如何抑制真菌病原体的，以及口腔状况（如不同疾病下唾液 pH 值的变化）是否会影响季铵盐的抗菌能力，这些都还不清楚。本研究评估了 DMADDM 在不同 pH 值下的体外和体内抗真菌效果。在浮游和生物膜生长中观察到 DMADDM 具有 pH 依赖性的抗真菌作用。DMADDM 在碱性 pH 下增强了抗真菌活性。白色念珠菌的两个 pH 调节基因（PHR1/PHR2）与 DMADDM 的 pH 依赖性抗真菌作用相关。PHR1/PHR2 基因和 pH 值调节了白色念珠菌的 ζ 电位，进而影响了白色念珠菌细胞与 DMADDM 的结合。在小鼠口咽念珠菌病模型中证实了 DMADDM 的 pH 依赖性抗真菌活性。我们直接证明了季铵盐的抗真菌能力依赖于细胞 ζ 电位，这影响了真菌细胞与季铵盐之间的结合。这些发现表明，在不同 pH 值下，季铵盐具有新的抗真菌机制，DMADDM 可以作为一种有潜力的抗真菌剂应用于牙科材料和口腔黏膜炎治疗。关键点 • DMADDM 在碱性 pH 条件下比在酸性 pH 条件下具有更强的抗真菌活性。 • pH 值和 pH 调节基因可以影响真菌细胞的 ζ 电位。 • 真菌细胞的 ζ 电位直接影响 DMADDM 与细胞之间的结合。图表抽象图显示了不同 pH 值下 DMADDM 的抗真菌活性。
