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Effects of Itraconazole and Micafungin on Aspergillus fumigatus Biofilms

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Abstract

Aspergillus fumigatus (A. fumigatus) is the most common airborne opportunistic fungal pathogen. Biofilm formation is one of the main pathogenic mechanisms of A. fumigatus. During the past decades, A. fumigatus azole resistance has become prevalent due to the medical and agricultural use of antifungal drugs and fungicides. Until now, the role of fungal biofilms in azole resistance of A. fumigatus remains unclear. In the present study, we compared biofilm drug susceptibility and biofilm formation under itraconazole of azole-resistant strains, sensitive strains, and standard strains, separately. The biofilm viability and matrix thickness at the early and the late stage were measured by XTT assay and Calcofluor white. Our results showed that the sessile minimum inhibitory concentration of itraconazole, which describing the inhibition of drugs on fungi sessile with biofilm, was much higher than the traditional minimal inhibitory concentration of itraconazole. Additionally, low concentrations of itraconazole inhibited biofilm formation of A. fumigatus strains. Notably, biofilm formation by azole-resistant strains could not be inhibited by high concentrations of itraconazole but could be effectively restrained by low concentrations of micafungin, revealing the efficacy of a cell-wall inhibitor to disrupt A. fumigatus biofilm formation. However, late-stage biofilms of both azole-resistant strains and standard strains were hard to disrupt using itraconazole. We found that itraconazole was effective to prevent A. fumigatus biofilm formation at the early stage. For the treatment of A. fumigatus biofilm, our findings suggest that an early-stage preventive strategy is preferred and micafungin is effective to control the azole-resistant strain infection.

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Acknowledgements

The research was supported by the National Natural Science Foundation of China (Grant No. 81501726), the Fundamental Research Funds for the Central Universities (Grant No. 2019XK32007), the Natural Science Foundation of Jiangsu Province (Grant No. BK20150069), the Major national science and technology projects (Grant No. 2019ZX09721001-006-003), the National Natural Science Foundation of China (Grant No. 81502739).

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Authors and Affiliations

  1. Institute of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College, 12 Jiangwangmiao Street, Nanjing, 210042, Jiangsu, China

    Musang Liu, Hailin Zheng, Rong Zeng, Guanzhao Liang & Weida Liu

  2. Medical School, Nanjing University, Nanjing, Jiangsu, China

    Nan Zheng

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  1. Musang Liu
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Liu, M., Zheng, H., Zeng, R. et al. Effects of Itraconazole and Micafungin on Aspergillus fumigatus Biofilms. Mycopathologia 186, 387–397 (2021). https://doi.org/10.1007/s11046-021-00534-4

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