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      Antifungal Activity of Linear and Disulfide-Cyclized Ultrashort Cationic Lipopeptides Alone and in Combination with Fluconazole against Vulvovaginal Candida spp.

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          Abstract

          Vulvovaginal candidiasis (VVC) occurs in over 75% of women at least once during their lifetime and is an infection that significantly affects their health. Candida strains resistant to standard azole antifungal therapy and relapses of VVC are more and more common. Hypothetically, biofilm is one of the main reasons of relapses and failure of the therapy. Ultrashort cationic lipopeptides (USCLs) exhibit high antimicrobial activities. Our previous study on USCLs revealed that disulfide cyclization can result in selective antifungal compounds. Therefore, four USCL were selected and their antifungal activity were studied on 62 clinical strains isolated from VVC. The results confirmed previous premises that cyclic analogs have increased selectivity between fungal cells and keratinocytes and improved anticandidal activity compared to their linear analogs against both planktonic and biofilm cultures. On the other hand, linear lipopeptides in combination with fluconazole showed a synergistic effect. It was found that the minimum inhibitory concentrations of the tested compounds in combination with fluconazole were at least four times lower than when used separately. Our results indicate that combination therapy of VVC with USCLs and fluconazole at low non-toxic concentrations can be beneficial owing to the synergistic effect. However, further in vivo studies are needed to confirm this hypothesis.

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          Author and article information

          Journal
          Pharmaceutics
          Pharmaceutics
          MDPI AG
          1999-4923
          1999-4923
          Sep 30 2021
          : 13
          : 10
          Affiliations
          [1 ] Department of Microbiology, Faculty of Medicine, Wrocław Medical University, 51-368 Wrocław, Poland.
          [2 ] Department of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdańsk, 80-210 Gdańsk, Poland.
          Article
          pharmaceutics13101589
          10.3390/pharmaceutics13101589
          8537571
          34683882
          d6454e5e-2046-4a69-9c71-2c444785039d
          History

          fluconazole,Candida,Vulvovaginal candidiasis,biofilm,cationic lipopeptides,lipopeptides,synergy

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