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聚(甲基丙烯酸)-银纳米粒子对氟康唑耐药白念珠菌菌株的活性:协同和细胞毒性作用。

Activity of poly(methacrylic acid)-silver nanoparticles on fluconazole-resistant Candida albicans strains: Synergistic and cytotoxic effects.

机构信息

Postgraduate Program in Dentistry, Federal University of Pernambuco, Recife, Brazil.

Department of Physics, Federal University of Pernambuco, Recife, Brazil.

出版信息

J Appl Microbiol. 2022 Jun;132(6):4300-4309. doi: 10.1111/jam.15542. Epub 2022 Mar 31.

DOI:10.1111/jam.15542
PMID:35338561
Abstract

AIMS

To synthesize and evaluate the antifungal activity of poly(methacrylic acid)-silver nanoparticles (PMAA-AgNPs) against nine Candida albicans isolated from clinical specimens.

METHODS AND RESULTS

The effects of PMAA-AgNPs-fluconazole combination was analysed by checkerboard methodology. The synergistic potential of PMAA-AgNPs-fluconazole was determined by the fractional inhibitory concentration index (FICI). The inhibition of germ tube formation and the determination of PMAA-AgNPs cytotoxicity were also performed. All C. albicans strains were susceptible to PMAA-AgNPs and resistant to fluconazole. PMAA-AgNPs at subinhibitory concentrations restored the susceptibility of resistant C. albicans to fluconazole, whose FICI ranged from 0.3 to 0.5. The synergistic interaction of the combination was observed in eight of nine strains. The PMAA-AgNPs-fluconazole combination was also able to inhibit the germ tube formation. PMAA-AgNPs showed a dose-dependent decrease in viability for cells tested, with 50% cytotoxic concentration (CC ) values of 6.5, 4.9 and 6.8 μg ml for macrophages, fibroblasts and Vero cells, respectively.

CONCLUSIONS

This study demonstrated that, in general, PMAA-AgNPs acts synergistically in combination with fluconazole, inhibiting fluconazole-resistant C. albicans strains. PMAA-AgNPs-fluconazole combination was also able to inhibit germ tube formation, an important virulence factor. Inhibitory effect of PMAA-AgNPs alone or in combination was higher in C. albicans than in mammalian cells.

SIGNIFICANCE AND IMPACT OF STUDY

This study shows the potential of PMAA-AgNPs combined with fluconazole to inhibit fluconazole-resistant C. albicans strains.

摘要

目的

合成并评估聚(甲基丙烯酸)-银纳米粒子(PMAA-AgNPs)对从临床标本中分离出的 9 株白色念珠菌的抗真菌活性。

方法和结果

采用棋盘微量稀释法分析 PMAA-AgNPs-氟康唑联合用药的效果。通过部分抑菌浓度指数(FICI)来确定 PMAA-AgNPs-氟康唑的协同潜力。还进行了芽管形成抑制实验和 PMAA-AgNPs 细胞毒性测定。所有白色念珠菌菌株均对 PMAA-AgNPs 敏感,对氟康唑耐药。PMAA-AgNPs 在亚抑菌浓度下恢复了耐药白色念珠菌对氟康唑的敏感性,其 FICI 范围为 0.3 至 0.5。在 9 株菌株中的 8 株中观察到联合用药的协同相互作用。PMAA-AgNPs-氟康唑联合用药也能抑制芽管形成。PMAA-AgNPs 对所测试的细胞表现出剂量依赖性的存活率降低,巨噬细胞、成纤维细胞和 Vero 细胞的 50%细胞毒性浓度(CC )值分别为 6.5、4.9 和 6.8μg/ml。

结论

本研究表明,一般来说,PMAA-AgNPs 与氟康唑联合使用具有协同作用,抑制氟康唑耐药白色念珠菌菌株。PMAA-AgNPs-氟康唑联合用药还能抑制芽管形成,这是一种重要的毒力因子。PMAA-AgNPs 单独或联合使用对白色念珠菌的抑制作用强于对哺乳动物细胞的抑制作用。

意义和影响

本研究表明,PMAA-AgNPs 与氟康唑联合使用具有抑制氟康唑耐药白色念珠菌菌株的潜力。

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