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Bacillomycin D effectively controls growth of Malassezia globosa by disrupting the cell membrane

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Abstract

Malassezia globosa is an opportunistic pathogen that causes various skin disorders, which disturbs people’s life all the time, and conventional drugs are not completely satisfactory. Bacillomycin D (BD), an antifungal lipopeptide, could inhibit various fungi growth. However, the reports about its effect on M. globosa were not found yet. In this study, we showed that BD and BD-C16 (fatty acid chain had sixteen carbon atoms) completely inhibited growth of M. globosa at concentration of 64 μg/ml in 15 h, which was confirmed with the observation of irregular morphological change of M. globosa treated with BD. Significantly, the study on the working mechanism showed that BD induced cell death by changing cell membrane permeability and thus promoting the release of cellular contents, which may be mediated by the interaction between BD and ergosterol from membrane. Further study showed that BD reduced the overall content of cellular sterol, and interestingly, the expression of some genes involved in membrane and ergosterol synthesis were significantly upregulated, which was likely to be a feedback regulation. Besides, we found that BD had additive and synergistic effects with ketoconazole and amphotericin B, respectively, on inhibition of M. globosa, suggesting that combination use of BD with other commercial drugs could be a promising strategy to relieve skin disorders caused by M. globosa.

Key Points

BD could efficiently inhibit the growth of M. globosa.

BD increases cell membrane permeability and thus promotes the release of cellular contents.

BD has additive or synergistic effect with other antifungal drugs.

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Funding

This work was supported by the National Natural and Science Foundation of China (No. 31771948).

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TW performed the experiments, analyzed the data, and wrote the manuscript. MC and LZ analyzed the data, and wrote the manuscript. FL and XB analyzed and discussed the data. ZL designed the research content, analyzed the data, and modified the manuscript. All authors read and approved the final manuscript.

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Correspondence to Zhaoxin Lu.

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Wu, T., Chen, M., Zhou, L. et al. Bacillomycin D effectively controls growth of Malassezia globosa by disrupting the cell membrane. Appl Microbiol Biotechnol 104, 3529–3540 (2020). https://doi.org/10.1007/s00253-020-10462-w

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