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基于RAFT的聚甲基丙烯酸酯通过靶向生物膜和持留菌细胞,作为复发性外阴阴道念珠菌病的一种卓越治疗方法。

RAFT-Derived Polymethacrylates as a Superior Treatment for Recurrent Vulvovaginal Candidiasis by Targeting Biotic Biofilms and Persister Cells.

作者信息

Wu Xueqing, Zhang Sisi, Xu Xinxin, Shen Laien, Xu Boyun, Qu Wenzhen, Zhuang Wenyi, Locock Katherine, Deighton Margaret, Qu Yue

机构信息

The Division of Gynecology, Shenzhen University General Hospital, Shenzhen, China.

Department of Obstetrics and Gynecology, Wenzhou Medical University, Wenzhou, China.

出版信息

Front Microbiol. 2019 Nov 7;10:2592. doi: 10.3389/fmicb.2019.02592. eCollection 2019.

Abstract

BACKGROUND

Vulvovaginal candidiasis (VVC) is a common infection in need of more effective treatment. Formation of epithelium-associated biofilms and the presence of persister cells are among the major contributing factors to the recurrence of this condition. We have previously developed RAFT-derived polymethacrylates that are effective in killing biofilms . This study aimed to examine the clinical potential of polymethacrylates as antifungals for treatment of recurrent VVC (RVVC).

METHODS

A mouse model of VVC was used to establish vaginal epithelium-associated biofilms, using isolates from VVC/RVVC patients. A comparison was made of the efficacies of polymethacrylates and conventional antifungals, clotrimazole and nystatin, in killing in epithelium-associated biofilms . biofilms were used for population profiling and to quantify persister cells in vaginal epithelia. The potency of polymethacrylates and conventional antifungals against persister cells, either as sole agents or in combination, was assessed.

RESULTS

Polymethacrylates showed negligible local toxicity, resistance to vaginal acidity, and outstanding activity against vaginal epithelium-associated biofilms. tests polymethacrylates outperformed the conventional antifungals, nystatin and clotrimazole at concentrations 50 times below the over-the-counter concentrations. Using polymethacrylates was associated with fewer persister cells, and better eradication of persister cells pre-selected by conventional antifungals.

CONCLUSION

This study systematically assessed the clinical potential of RAFT-derived polymethacrylates as an effective treatment for VVC/RVVC in a mouse model. Polymethacrylates effectively killed vaginal epithelium-related by specially targeting biotic biofilms and persister cells. Treatment presented negligible local toxicity.

摘要

背景

外阴阴道念珠菌病(VVC)是一种常见感染,需要更有效的治疗方法。上皮相关生物膜的形成和持续存在的细胞是导致这种疾病复发的主要因素。我们之前开发了源自可逆加成-断裂链转移(RAFT)的聚甲基丙烯酸酯,其对生物膜具有杀灭作用。本研究旨在探讨聚甲基丙烯酸酯作为抗真菌药物治疗复发性外阴阴道念珠菌病(RVVC)的临床潜力。

方法

使用VVC/RVVC患者的分离株,通过VVC小鼠模型建立阴道上皮相关生物膜。比较了聚甲基丙烯酸酯与传统抗真菌药物克霉唑和制霉菌素对上皮相关生物膜的杀灭效果。利用生物膜进行群体分析并定量阴道上皮中的持续存在细胞。评估了聚甲基丙烯酸酯和传统抗真菌药物单独或联合对持续存在细胞的效力。

结果

聚甲基丙烯酸酯显示出可忽略不计的局部毒性、对阴道酸度的耐受性,以及对阴道上皮相关生物膜的出色活性。测试表明聚甲基丙烯酸酯在浓度低于非处方浓度50倍时优于传统抗真菌药物制霉菌素和克霉唑。使用聚甲基丙烯酸酯可减少持续存在细胞的数量,并能更好地根除经传统抗真菌药物预先选择的持续存在细胞。

结论

本研究在小鼠模型中系统评估了源自RAFT的聚甲基丙烯酸酯作为VVC/RVVC有效治疗方法的临床潜力。聚甲基丙烯酸酯通过特异性靶向生物膜和持续存在细胞有效地杀灭阴道上皮相关生物膜。治疗显示出可忽略不计的局部毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff74/6853869/c9343c8c67c1/fmicb-10-02592-g001.jpg

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