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Cytochalasans Act as Inhibitors of Biofilm Formation of Staphylococcus aureus

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Department Chemical Microbiology, Helmholtz Centre for Infection Research (HZI), Inhoffenstraße 7, 38124 Braunschweig, Germany
2
Department Microbial Drugs, Helmholtz Centre for Infection Research (HZI), Inhoffenstraße 7, 38124 Braunschweig, Germany
3
National Centre for Genetic Engineering and Biotechnology (BIOTEC), NSTDA, 113 Thailand Science Park, Phahonyothin Road, Klong Nueng, Klong Luang, Pathum Thani 12120, Thailand
*
Author to whom correspondence should be addressed.
Biomolecules 2018, 8(4), 129; https://doi.org/10.3390/biom8040129
Received: 27 September 2018 / Revised: 29 October 2018 / Accepted: 29 October 2018 / Published: 30 October 2018
During the course of our ongoing work to discover new inhibitors of biofilm formation of Staphylococcus aureus from fungal sources, we observed biofilm inhibition by cytochalasans isolated from cultures of the ascomycete Hypoxylon fragiforme for the first time. Two new compounds were purified by a bioassay-guided fractionation procedure; their structures were elucidated subsequently by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). This unexpected finding prompted us to test further cytochalasans from other fungi and from commercial sources for comparison. Out of 21 cytochalasans, 13 showed significant inhibition of Staphylococcus aureus biofilm formation at subtoxic levels. These findings indicate the potential of cytochalasans as biofilm inhibitors for the first time, also because the minimum inhibitory concentrations (MIC) are independent of the anti-biofilm activities. However, cytochalasans are known to be inhibitors of actin, making some of them very toxic for eukaryotic cells. Since the chemical structures of the tested compounds were rather diverse, the inclusion of additional derivatives, as well as the evaluation of their selectivity against mammalian cells vs. the bacterium, will be necessary as next step in order to develop structure-activity relationships and identify the optimal candidates for development of an anti-biofilm agent. View Full-Text
Keywords: ascomycota; bacterial pathogens; biofilm dispersion; chromatography; natural products; secondary metabolites; structure elucidation; Xylariales ascomycota; bacterial pathogens; biofilm dispersion; chromatography; natural products; secondary metabolites; structure elucidation; Xylariales
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Yuyama, K.T.; Wendt, L.; Surup, F.; Kretz, R.; Chepkirui, C.; Wittstein, K.; Boonlarppradab, C.; Wongkanoun, S.; Luangsa-ard, J.; Stadler, M.; Abraham, W.-R. Cytochalasans Act as Inhibitors of Biofilm Formation of Staphylococcus aureus. Biomolecules 2018, 8, 129.

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