Department of Biology, University of Naples "Federico II", via Cinthia, 80100, Naples, Italy.
Department of Pharmacy, University of Naples "Federico II", Via Mezzocannone 16, 80134, Naples, Italy.
Sci Rep. 2020 Apr 1;10(1):5780. doi: 10.1038/s41598-020-62746-w.
Biofilm formation poses an important clinical trouble due to resistance to antimicrobial agents; therefore, there is an urgent demand for new antibiofilm strategies that focus on the use of alternative compounds also in combination with conventional drugs. Drug-tolerant persisters are present in Candida albicans biofilms and are detected following treatment with high doses of amphotericin B. In this study, persisters were found in biofilms treated with amphotericin B of two clinical isolate strains, and were capable to form a new biofilm in situ. We investigated the possibility of eradicating persister-derived biofilms from these two Candida albicans strains, using the peptide gH625 analogue (gH625-M). Confocal microscopy studies allowed us to characterize the persister-derived biofilm and understand the mechanism of interaction of gH625-M with the biofilm. These findings confirm that persisters may be responsible for Candida biofilm survival, and prove that gH625-M was very effective in eradicating persister-derived biofilms both alone and in combination with conventional antifungals, mainly strengthening the antibiofilm activity of fluconazole and 5-flucytosine. Our strategy advances our insights into the development of effective antibiofilm therapeutic approaches.
生物膜的形成会对抗菌药物产生抗药性，从而导致重要的临床问题；因此，人们迫切需要新的抗生物膜策略，这些策略侧重于使用替代化合物，也可以与传统药物联合使用。耐药物的持久性生物被存在于白色念珠菌生物膜中，并在高剂量两性霉素 B 治疗后被检测到。在这项研究中，在两种临床分离株的两性霉素 B 处理的生物膜中发现了持久性生物，并且能够在原位形成新的生物膜。我们使用肽 gH625 类似物（gH625-M）研究了从这两种白色念珠菌菌株中根除持久性生物膜的可能性。共聚焦显微镜研究使我们能够对持久性生物膜进行特征描述，并了解 gH625-M 与生物膜相互作用的机制。这些发现证实了持久性生物可能是导致白色念珠菌生物膜存活的原因，并证明 gH625-M 单独使用和与传统抗真菌药物联合使用时，都非常有效地根除持久性生物膜，主要增强了氟康唑和 5-氟胞嘧啶的抗生物膜活性。我们的策略深入了解了开发有效抗生物膜治疗方法的潜力。
