Cytochalasans Act as Inhibitors of Biofilm Formation of <i>Staphylococcus aureus</i>

During the course of our ongoing work to discover new inhibitors of biofilm formation of <i>Staphylococcus aureus</i> from fungal sources, we observed biofilm inhibition by cytochalasans isolated from cultures of the ascomycete <i>Hypoxylon fragiforme</i> for the first time....

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Main Authors: Kamila Tomoko Yuyama, Lucile Wendt, Frank Surup, Robin Kretz, Clara Chepkirui, Kathrin Wittstein, Chollaratt Boonlarppradab, Sarunyou Wongkanoun, Jennifer Luangsa-ard, Marc Stadler, Wolf-Rainer Abraham
Format: Article
Language:English
Published: MDPI AG 2018-10-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/8/4/129
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author Kamila Tomoko Yuyama
Lucile Wendt
Frank Surup
Robin Kretz
Clara Chepkirui
Kathrin Wittstein
Chollaratt Boonlarppradab
Sarunyou Wongkanoun
Jennifer Luangsa-ard
Marc Stadler
Wolf-Rainer Abraham
author_facet Kamila Tomoko Yuyama
Lucile Wendt
Frank Surup
Robin Kretz
Clara Chepkirui
Kathrin Wittstein
Chollaratt Boonlarppradab
Sarunyou Wongkanoun
Jennifer Luangsa-ard
Marc Stadler
Wolf-Rainer Abraham
author_sort Kamila Tomoko Yuyama
collection DOAJ
description During the course of our ongoing work to discover new inhibitors of biofilm formation of <i>Staphylococcus aureus</i> from fungal sources, we observed biofilm inhibition by cytochalasans isolated from cultures of the ascomycete <i>Hypoxylon fragiforme</i> 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 <i>Staphylococcus aureus</i> 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.
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spelling doaj.art-a65d3b900e954cc8930224b71ce2b5fe2022-12-21T18:52:30ZengMDPI AGBiomolecules2218-273X2018-10-018412910.3390/biom8040129biom8040129Cytochalasans Act as Inhibitors of Biofilm Formation of <i>Staphylococcus aureus</i>Kamila Tomoko Yuyama0Lucile Wendt1Frank Surup2Robin Kretz3Clara Chepkirui4Kathrin Wittstein5Chollaratt Boonlarppradab6Sarunyou Wongkanoun7Jennifer Luangsa-ard8Marc Stadler9Wolf-Rainer Abraham10Department Chemical Microbiology, Helmholtz Centre for Infection Research (HZI), Inhoffenstraße 7, 38124 Braunschweig, GermanyDepartment Microbial Drugs, Helmholtz Centre for Infection Research (HZI), Inhoffenstraße 7, 38124 Braunschweig, GermanyDepartment Microbial Drugs, Helmholtz Centre for Infection Research (HZI), Inhoffenstraße 7, 38124 Braunschweig, GermanyDepartment Microbial Drugs, Helmholtz Centre for Infection Research (HZI), Inhoffenstraße 7, 38124 Braunschweig, GermanyDepartment Microbial Drugs, Helmholtz Centre for Infection Research (HZI), Inhoffenstraße 7, 38124 Braunschweig, GermanyDepartment Microbial Drugs, Helmholtz Centre for Infection Research (HZI), Inhoffenstraße 7, 38124 Braunschweig, GermanyNational Centre for Genetic Engineering and Biotechnology (BIOTEC), NSTDA, 113 Thailand Science Park, Phahonyothin Road, Klong Nueng, Klong Luang, Pathum Thani 12120, ThailandNational Centre for Genetic Engineering and Biotechnology (BIOTEC), NSTDA, 113 Thailand Science Park, Phahonyothin Road, Klong Nueng, Klong Luang, Pathum Thani 12120, ThailandNational Centre for Genetic Engineering and Biotechnology (BIOTEC), NSTDA, 113 Thailand Science Park, Phahonyothin Road, Klong Nueng, Klong Luang, Pathum Thani 12120, ThailandDepartment Microbial Drugs, Helmholtz Centre for Infection Research (HZI), Inhoffenstraße 7, 38124 Braunschweig, GermanyDepartment Chemical Microbiology, Helmholtz Centre for Infection Research (HZI), Inhoffenstraße 7, 38124 Braunschweig, GermanyDuring the course of our ongoing work to discover new inhibitors of biofilm formation of <i>Staphylococcus aureus</i> from fungal sources, we observed biofilm inhibition by cytochalasans isolated from cultures of the ascomycete <i>Hypoxylon fragiforme</i> 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 <i>Staphylococcus aureus</i> 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.https://www.mdpi.com/2218-273X/8/4/129ascomycotabacterial pathogensbiofilm dispersionchromatographynatural productssecondary metabolitesstructure elucidationXylariales
spellingShingle Kamila Tomoko Yuyama
Lucile Wendt
Frank Surup
Robin Kretz
Clara Chepkirui
Kathrin Wittstein
Chollaratt Boonlarppradab
Sarunyou Wongkanoun
Jennifer Luangsa-ard
Marc Stadler
Wolf-Rainer Abraham
Cytochalasans Act as Inhibitors of Biofilm Formation of <i>Staphylococcus aureus</i>
Biomolecules
ascomycota
bacterial pathogens
biofilm dispersion
chromatography
natural products
secondary metabolites
structure elucidation
Xylariales
title Cytochalasans Act as Inhibitors of Biofilm Formation of <i>Staphylococcus aureus</i>
title_full Cytochalasans Act as Inhibitors of Biofilm Formation of <i>Staphylococcus aureus</i>
title_fullStr Cytochalasans Act as Inhibitors of Biofilm Formation of <i>Staphylococcus aureus</i>
title_full_unstemmed Cytochalasans Act as Inhibitors of Biofilm Formation of <i>Staphylococcus aureus</i>
title_short Cytochalasans Act as Inhibitors of Biofilm Formation of <i>Staphylococcus aureus</i>
title_sort cytochalasans act as inhibitors of biofilm formation of i staphylococcus aureus i
topic ascomycota
bacterial pathogens
biofilm dispersion
chromatography
natural products
secondary metabolites
structure elucidation
Xylariales
url https://www.mdpi.com/2218-273X/8/4/129
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