Cytochalasans Act as Inhibitors of Biofilm Formation of Staphylococcus Aureus

Abstract

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.

A novel species and a new combination of Daldinia from Ban Hua Thung community forest in the northern part of Thailand

“…The major cytochalasins in the stromata of the Thai specimens were recently identified as the new phenochalasins C and D (Figs. 3 and 4) and found to exhibit significant anti-biofilm effects in Staphylococcus aureus (Yuyama et al 2018). MB828032 Etymology.…”

“…For chemotaxonomic studies, the natural products were extracted using the method by Yuyama et al (2018), using high performance liquid chromatography coupled with diode array and electrospray mass spectrometric detection (HPLC/DAD-ESIMS). The instrumental settings and conditions were as described in Kuhnert et al (2017).…”

Diversely Functionalised Cytochalasins through Mutasynthesis and Semi‐Synthesis

“…In particular, cytochalasans [2] selectively bind the barbed ends of filamentous (F) actin [3, 4] . Many of the biological roles of the cytochalasans can be traced to this function, but antiviral [5] and antibiofilm [6] properties point to the likelihood of other targets in eukaryotes and prokaryotes, and characterisation of the inhibition of glucose transport in eukaryotes [7] suggests that their targets may be more diverse. Cytochalasans are generally produced by fermentation, and although hundreds of individual structures have been reported, [8] relatively few are available commercially.…”

Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica

“…Compounds that had shown inhibition of biofilm formation against either S. aureus or P. aeruginosa were further evaluated for their bacteriostatic and bactericidal activities, as described by Yuyama and co-workers [53], in 8 concentrations, ranging from 1.95-250 µg/mL. The assay was performed with each concentration tested in quadruplicates.…”