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.
Highlights
Biofilm infections are a serious threat in hospitals; following the data of Centers for Disease Control and Prevention Report (2007) [1], around 1.7 million of infections occur per year and 99,000 deaths are caused by infections associated with biofilms
We report for the first time an activity of these compounds against biofilm formation of the prokaryotic S. aureus
minimum inhibitory concentrations (MIC) were independent of the biofilm inhibitions, indicating that the compounds only inhibit the biofilm formation but did not kill the bacterium
Summary
Biofilm infections are a serious threat in hospitals; following the data of Centers for Disease Control and Prevention Report (2007) [1], around 1.7 million of infections occur per year and 99,000 deaths are caused by infections associated with biofilms. Biomolecules 2018, 8, 129 endocarditis, ocular infections and in polymicrobial biofilm infections Beyond that, this pathogen is often resistant to antibiotics, increases the infection in indwelling medical devices and contributes to nosocomial infections [3]. The rational assumption is that fungi grow in a wet environment propitious for biofilm development; they have developed strategies to protect themselves against biofilms. One of these strategies could be the biosynthesis of secondary metabolites that act as inhibitors of quorum sensing, i.e., the communication of microorganisms through small molecules that coordinate the virulence, formation and maintenance of biofilms [8]
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