Promising class of compounds as inhibitors of biofilm formation

Cytochalasans can inhibit S. aureus biofilms

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Yuyama and colleagues published the discovery of new cytochalasans, isolated from cultures of Hypoxylon fragiforme for the first time. The researchers stated that 13 compounds presented significant inhibition of Staphylococcus aureus biofilm formation at subtoxic levels, demonstrating the potential of cytochalasans as biofilm inhibitors. The inclusion of additional derivatives, and the performance of toxicity tests will be the next step, in order to evaluate the structure-activity and identify the best molecules for the development of an anti-biofilm agent. 

Good to know...

  • fungal metabolites
  • name is derived from Greek: κύτοςkytos, cell; χάλασιςchalasis, relaxation
  • effect: influence on actin filament networks in eukaryotic cells, resulting in a deterioration of the dynamic processes involving the cytoskeleton formation
  • have a wide range of biological activities, representing a group of potential drug candidates, especially as anticancer agents

(Brase et al., 2012)

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. 

Reference: Yuyama KT, Wendt L , Surup F, Kretz R, Chepkirui C, Wittstein K, Boonlarppradab C, Wongkanoun S, Luangsa-Ard J, Stadler M, Abraham WR. Cytochalasans Act as Inhibitors of Biofilm Formation of Staphylococcus Aureus. Biomolecules, 2018;8(4). doi: 10.3390/biom8040129

Celia Fortuna Rodrigues

PharmD, PhD , University of Porto


Go to the profile of IQBAL AHMAD
about 3 years ago

New information on biofilm inhibitor


Go to the profile of Celia Fortuna Rodrigues
about 3 years ago

Yes, it is :)