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

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

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.02592

DOI=10.3389/fmicb.2019.02592

ISSN=1664-302X

ABSTRACT=<sec><title>Background</title><p>Vulvovaginal candidiasis (VVC) is a common infection in need of more effective treatment. Formation of epithelium-associated <italic>Candida</italic> 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 <italic>C. albicans</italic> biofilms <italic>in vitro</italic>. This study aimed to examine the clinical potential of polymethacrylates as antifungals for treatment of recurrent VVC (RVVC).</p></sec><sec><title>Methods</title><p>A mouse model of VVC was used to establish vaginal epithelium-associated biofilms, using <italic>C. albicans</italic> isolates from VVC/RVVC patients. A comparison was made of the efficacies of polymethacrylates and conventional antifungals, clotrimazole and nystatin, in killing <italic>Candida</italic> in epithelium-associated biofilms <italic>in vivo</italic>. <italic>Ex vivo</italic> biofilms were used for <italic>Candida</italic> 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.</p></sec><sec><title>Results</title><p>Polymethacrylates showed negligible local toxicity, resistance to vaginal acidity, and outstanding <italic>in vivo</italic> activity against vaginal epithelium-associated <italic>C. albicans</italic> biofilms. <italic>In vivo</italic> 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.</p></sec><sec><title>Conclusion</title><p>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 <italic>C. albicans in vivo</italic> by specially targeting biotic biofilms and persister cells. Treatment presented negligible local toxicity.</p></sec>