RAFT-Derived Polymethacrylates as a Superior Treatment for Recurrent Vulvovaginal Candidiasis by Targeting Biotic Biofilms and Persister Cells
BackgroundVulvovaginal candidiasis (VVC) is a common infection in need of more effective treatment. Formation of epithelium-associated Candida biofilms and the presence of persister cells are among the major contributing factors to the recurrence of this condition. We have previously developed RAFT-...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.02592/full |
| _version_ | 1818985482907811840 |
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| author | Xueqing Wu Xueqing Wu Sisi Zhang Xinxin Xu Laien Shen Boyun Xu Wenzhen Qu Wenyi Zhuang Katherine Locock Katherine Locock Margaret Deighton Yue Qu Yue Qu |
| author_facet | Xueqing Wu Xueqing Wu Sisi Zhang Xinxin Xu Laien Shen Boyun Xu Wenzhen Qu Wenyi Zhuang Katherine Locock Katherine Locock Margaret Deighton Yue Qu Yue Qu |
| author_sort | Xueqing Wu |
| collection | DOAJ |
| description | BackgroundVulvovaginal candidiasis (VVC) is a common infection in need of more effective treatment. Formation of epithelium-associated Candida 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 C. albicans biofilms in vitro. This study aimed to examine the clinical potential of polymethacrylates as antifungals for treatment of recurrent VVC (RVVC).MethodsA mouse model of VVC was used to establish vaginal epithelium-associated biofilms, using C. albicans isolates from VVC/RVVC patients. A comparison was made of the efficacies of polymethacrylates and conventional antifungals, clotrimazole and nystatin, in killing Candida in epithelium-associated biofilms in vivo. Ex vivo biofilms were used for Candida 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.ResultsPolymethacrylates showed negligible local toxicity, resistance to vaginal acidity, and outstanding in vivo activity against vaginal epithelium-associated C. albicans biofilms. In vivo 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.ConclusionThis 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 C. albicans in vivo by specially targeting biotic biofilms and persister cells. Treatment presented negligible local toxicity. |
| first_indexed | 2024-12-20T18:35:36Z |
| format | Article |
| id | doaj.art-612176e0ecc940618004ca70dc3ee3cd |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-20T18:35:36Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-612176e0ecc940618004ca70dc3ee3cd2022-12-21T19:29:55ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-11-011010.3389/fmicb.2019.02592492524RAFT-Derived Polymethacrylates as a Superior Treatment for Recurrent Vulvovaginal Candidiasis by Targeting Biotic Biofilms and Persister CellsXueqing Wu0Xueqing Wu1Sisi Zhang2Xinxin Xu3Laien Shen4Boyun Xu5Wenzhen Qu6Wenyi Zhuang7Katherine Locock8Katherine Locock9Margaret Deighton10Yue Qu11Yue Qu12The Division of Gynecology, Shenzhen University General Hospital, Shenzhen, ChinaDepartment of Obstetrics and Gynecology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Obstetrics and Gynecology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Obstetrics and Gynecology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Obstetrics and Gynecology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Obstetrics and Gynecology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Obstetrics and Gynecology, Wenzhou Medical University, Wenzhou, ChinaThe Division of Gynecology, Shenzhen University General Hospital, Shenzhen, ChinaCSIRO Manufacturing Flagship, Clayton, VIC, AustraliaSchool of Chemical and Biomedical Engineering, The University of Melbourne, Melbourne, VIC, AustraliaSchool of Applied Sciences, RMIT University, Bundoora, VIC, AustraliaNeonatal Intensive Care Unit, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Microbiology, Monash University, Clayton, VIC, AustraliaBackgroundVulvovaginal candidiasis (VVC) is a common infection in need of more effective treatment. Formation of epithelium-associated Candida 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 C. albicans biofilms in vitro. This study aimed to examine the clinical potential of polymethacrylates as antifungals for treatment of recurrent VVC (RVVC).MethodsA mouse model of VVC was used to establish vaginal epithelium-associated biofilms, using C. albicans isolates from VVC/RVVC patients. A comparison was made of the efficacies of polymethacrylates and conventional antifungals, clotrimazole and nystatin, in killing Candida in epithelium-associated biofilms in vivo. Ex vivo biofilms were used for Candida 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.ResultsPolymethacrylates showed negligible local toxicity, resistance to vaginal acidity, and outstanding in vivo activity against vaginal epithelium-associated C. albicans biofilms. In vivo 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.ConclusionThis 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 C. albicans in vivo by specially targeting biotic biofilms and persister cells. Treatment presented negligible local toxicity.https://www.frontiersin.org/article/10.3389/fmicb.2019.02592/fullRVVCmouse modelantifungal treatmentRAFT-derived polymethacrylatesbiotic biofilmspersister cells |
| spellingShingle | Xueqing Wu Xueqing Wu Sisi Zhang Xinxin Xu Laien Shen Boyun Xu Wenzhen Qu Wenyi Zhuang Katherine Locock Katherine Locock Margaret Deighton Yue Qu Yue Qu RAFT-Derived Polymethacrylates as a Superior Treatment for Recurrent Vulvovaginal Candidiasis by Targeting Biotic Biofilms and Persister Cells Frontiers in Microbiology RVVC mouse model antifungal treatment RAFT-derived polymethacrylates biotic biofilms persister cells |
| title | RAFT-Derived Polymethacrylates as a Superior Treatment for Recurrent Vulvovaginal Candidiasis by Targeting Biotic Biofilms and Persister Cells |
| title_full | RAFT-Derived Polymethacrylates as a Superior Treatment for Recurrent Vulvovaginal Candidiasis by Targeting Biotic Biofilms and Persister Cells |
| title_fullStr | RAFT-Derived Polymethacrylates as a Superior Treatment for Recurrent Vulvovaginal Candidiasis by Targeting Biotic Biofilms and Persister Cells |
| title_full_unstemmed | RAFT-Derived Polymethacrylates as a Superior Treatment for Recurrent Vulvovaginal Candidiasis by Targeting Biotic Biofilms and Persister Cells |
| title_short | RAFT-Derived Polymethacrylates as a Superior Treatment for Recurrent Vulvovaginal Candidiasis by Targeting Biotic Biofilms and Persister Cells |
| title_sort | raft derived polymethacrylates as a superior treatment for recurrent vulvovaginal candidiasis by targeting biotic biofilms and persister cells |
| topic | RVVC mouse model antifungal treatment RAFT-derived polymethacrylates biotic biofilms persister cells |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.02592/full |
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