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杆菌霉素D及其与两性霉素B的组合:具有强大抗生物膜活性和伤口愈合潜力的有前景的抗真菌化合物。

Bacillomycin D and its combination with amphotericin B: promising antifungal compounds with powerful antibiofilm activity and wound-healing potency.

作者信息

Tabbene O, Azaiez S, Di Grazia A, Karkouch I, Ben Slimene I, Elkahoui S, Alfeddy M N, Casciaro B, Luca V, Limam F, Mangoni M L

机构信息

Laboratoire des Substances Bioactives, Centre de Biotechnologie de Borj-Cedria, Hammam-Lif, Tunisia.

Dipartimento di Scienze Biochimiche, Istituto Pasteur-Fondazione Cenci Bolognetti, Universita' La Sapienza, Rome, Italy.

出版信息

J Appl Microbiol. 2016 Feb;120(2):289-300. doi: 10.1111/jam.13030.

Abstract

AIMS

In this study, we evaluated the ability of the lipopeptide bacillomycin D and the antifungal drug amphotericin B as well as their combination, to inhibit Candida albicans biofilm formation and to accelerate keratinocyte cell migration.

METHODS AND RESULTS

The antibiofilm activity of bacillomycin D and its combination with amphotericin B was carried out by crystal violet colorimetric method. Our results have shown that, when combined together at low concentrations nontoxic to mammalian cells, corresponding to 1/32 MIC (0·39 μg ml(-1) ) and 1/4 MIC (0·06 μg ml(-1) ) for bacillomycin D and amphotericin B, respectively, a clear antibiofilm activity is manifested (95% inhibition of biofilm formation) along with a clear inhibition of germ tube formation. Moreover, the effect of both drugs on preformed biofilm of C. albicans strain was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The combination of the two antifungal compounds at 0·39 and 1 μg ml(-1) for bacillomycin D and amphotericin B, respectively, resulted in a clear enhancement of biofilm eradication compared to the results obtained with each drug alone. Furthermore, this combination was found to promote the closure of a gap produced in a monolayer of human keratinocytes.

CONCLUSIONS

Bacillomycin D and its combination with amphotericin B display impressive anti-biofilm and wound-healing activities.

SIGNIFICANCE AND IMPACT OF THE STUDY

Application of the lipopeptide bacillomycin D and the antifungal drug amphotericin B in medical devices may offer a promising alternative for topical treatment of Candida-associated infections in the setting of a wound.

摘要

目的

在本研究中,我们评估了脂肽杆菌霉素D、抗真菌药物两性霉素B及其组合抑制白色念珠菌生物膜形成和加速角质形成细胞迁移的能力。

方法与结果

采用结晶紫比色法检测杆菌霉素D及其与两性霉素B组合的抗生物膜活性。我们的结果表明,当以对哺乳动物细胞无毒的低浓度组合时,杆菌霉素D和两性霉素B分别对应1/32 MIC(0·39μg/ml)和1/4 MIC(0·06μg/ml),表现出明显的抗生物膜活性(生物膜形成抑制率达95%)以及对芽管形成的明显抑制。此外,使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)还原试验测定了两种药物对白色念珠菌菌株预先形成的生物膜的影响。杆菌霉素D和两性霉素B分别以0·39和1μg/ml的浓度组合,与单独使用每种药物相比,生物膜清除效果明显增强。此外,发现这种组合可促进人角质形成细胞单层中产生的间隙闭合。

结论

杆菌霉素D及其与两性霉素B的组合具有显著的抗生物膜和伤口愈合活性。

研究的意义和影响

脂肽杆菌霉素D和抗真菌药物两性霉素B在医疗器械中的应用可能为伤口环境中念珠菌相关感染的局部治疗提供一种有前景的替代方法。

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