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七叶皂苷单独或与抗真菌药物联合使用对耐药生物膜的影响:作用机制

Effect of Escin Alone or in Combination with Antifungal Agents on Resistant Biofilms: Mechanisms of Action.

作者信息

Maione Angela, Imparato Marianna, Galdiero Marilena, Alteriis Elisabetta de, Feola Antonia, Galdiero Emilia, Guida Marco

机构信息

Department of Biology, University of Naples 'Federico II', Via Cinthia, 80126 Naples, Italy.

Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 81100 Naples, Italy.

出版信息

Antibiotics (Basel). 2023 Jul 20;12(7):1210. doi: 10.3390/antibiotics12071210.

DOI:10.3390/antibiotics12071210
PMID:37508306
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10376425/
Abstract

Nowadays, the increase in antimicrobial-resistant fungi (AMR) is certainly a major health concern, and the development of alternative therapeutic strategies has become crucial. Natural products have been used to treat various infections, and their chemical properties contribute to the performance of their biological activities, such as antifungal action. The various virulence factors and mechanisms of resistance to antifungals contribute to making one of the most frequent agents of candidiasis. Here we investigate the in vitro and in vivo activity of β-escin against . The β-escin MICs were determined for a reference strain and two clinical isolates of . Furthermore, growth kinetics assays and biofilm inhibition/eradication assays (crystal violet) were performed. The differences in the expression of some anti-biofilm-associated genes were analyzed during biofilm inhibition treatment so that reactive oxygen species could be detected. The efficacy of β-escin was evaluated in combination with fluconazole, ketoconazole, and itraconazole. In addition, a infection model was used for in vivo treatment assays. Results have shown that β-escin had no toxicity in vitro or in vivo and was able to inhibit or destroy biofilm formation by downregulating some important genes, inducing ROS activity and affecting the membrane integrity of cells. Furthermore, our study suggests that the combination with azoles can have synergistic effects against biofilm. In summary, the discovery of new antifungal drugs against these resistant fungi is crucial and could potentially lead to the development of future treatment strategies.

摘要

如今,耐抗菌真菌(AMR)的增加无疑是一个主要的健康问题,开发替代治疗策略变得至关重要。天然产物已被用于治疗各种感染,其化学性质有助于其生物活性的发挥,如抗真菌作用。各种毒力因子和抗真菌耐药机制导致念珠菌病成为最常见的病原体之一。在这里,我们研究了β-七叶皂苷对……的体外和体内活性。测定了一株参考菌株和两株……临床分离株的β-七叶皂苷最低抑菌浓度(MIC)。此外,还进行了生长动力学测定和生物膜抑制/根除测定(结晶紫法)。在生物膜抑制治疗期间分析了一些抗生物膜相关基因表达的差异,以便检测活性氧。评估了β-七叶皂苷与氟康唑、酮康唑和伊曲康唑联合使用的效果。此外,使用……感染模型进行体内治疗试验。结果表明,β-七叶皂苷在体外和体内均无毒性,能够通过下调一些重要基因、诱导活性氧活性和影响……细胞的膜完整性来抑制或破坏生物膜形成。此外,我们的研究表明,与唑类药物联合使用对……生物膜可能具有协同作用。总之,发现针对这些耐药真菌的新型抗真菌药物至关重要,可能会推动未来治疗策略的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/f502192024e3/antibiotics-12-01210-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/49e4d2f9c2f6/antibiotics-12-01210-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/388a9db70023/antibiotics-12-01210-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/2085814bc432/antibiotics-12-01210-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/a9db47a2070e/antibiotics-12-01210-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/ea1f02713d6d/antibiotics-12-01210-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/6edc9287a584/antibiotics-12-01210-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/111c4ca4585d/antibiotics-12-01210-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/f502192024e3/antibiotics-12-01210-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/49e4d2f9c2f6/antibiotics-12-01210-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/388a9db70023/antibiotics-12-01210-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/2085814bc432/antibiotics-12-01210-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/a9db47a2070e/antibiotics-12-01210-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/ea1f02713d6d/antibiotics-12-01210-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/6edc9287a584/antibiotics-12-01210-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/111c4ca4585d/antibiotics-12-01210-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6df7/10376425/f502192024e3/antibiotics-12-01210-g008.jpg

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