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.

中文翻译：

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甲基丙烯酸二甲基氨基十二烷基酯以pH依赖的方式抑制白色念珠菌和口咽念珠菌病。

口腔炎的流行，尤其是由白色念珠菌引起的口腔炎，凸显了对新型抗真菌药的需求。我们以前发现，掺入牙科材料中的一种季铵盐甲基丙烯酸二甲基氨基十二烷基酯（DMADDM）抑制白色念珠菌的生长和菌丝发育。然而，季铵盐如何抑制真菌病原体以及口腔状况（例如不同疾病下唾液pH的变化）是否会影响季铵盐的抗菌能力尚不清楚。这项研究评估了DMADDM在体外和体内在不同pH下的抗真菌作用。在浮游生物膜和生物膜的生长中观察到DMADDM的pH依赖性抗真菌作用。DMADDM在碱性pH值下增强了抗真菌活性。C的两个pH调节基因（PHR1 / PHR2）。白色念珠菌与DMADDM的pH依赖性抗真菌作用有关。PHR1 / PHR2基因和pH值调节白色念珠菌的ζ电位，然后影响白色念珠菌细胞与DMADDM之间的结合。然后在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zeta电位，该电位影响真菌细胞与季铵盐之间的结合。这些发现提示了在不同pH值下季铵盐具有抗真菌作用的新机理，并且DMADDM可能是在牙科材料和口腔炎治疗中应用的潜在抗真菌剂。要点•DMADDM在碱性条件下比在酸性pH条件下具有更强的抗真菌活性。•pH值和pH调节基因会影响真菌细胞的Zeta电位。•真菌细胞的Zeta电位直接影响DMADDM与细胞之间的结合。DMADDM在不同pH值下的抗真菌活性的图形摘要示意图。