Such a “”proof of concept”" has already been provided by mimics of the acylated homoserine lactone signalling molecules, such as synthetic derivatives of natural furanones, which are able to inhibit in vivo biofilm development of Pseudomonas aeruginosa [13], and when covalently bound to surfaces BKM120 also those of Staphylococcus epidermidis [14]. Moreover the quorum-sensing RNA III inhibiting peptide was shown to inhibit in vivo biofilm formation of Staphylococcus aureus [15]. However none of the quorum sensing blockers tested in animal models so far was suitable for human use. Our project is aimed at finding new inhibitors

of biofilm formation of the Gram-positive facultative anaerobic bacterium S. mutans. Among more than 500 bacterial species found in dental plaque [16–18]S. mutans is considered to be the principal pathogen causing human dental caries [19]. While metabolising dietary carbohydrates, S. mutans rapidly produces acid endproducts lowering the pH to approximately pH 3.5 resulting in demineralisation

of the dental enamel and caries formation [20–22]. Moreover S. mutans can be a cause of subacute infective endocarditis [19, 23]. We focused in our search for biofilm inhibitors on our ATM/ATR inhibitor clinical trial collection of secondary metabolites from myxobacteria. They are ubiquitous Gram-negative soil bacteria characterized by their ability to glide in swarms, as well as by their complex life cycle that upon starvation culminates in the formation of multicellular fruiting bodies, containing dormant myxospores [24]. The complexity of their social behaviour and morphogenetic potential is reflected in their large genomes Chlormezanone (9-13 Mbp), some of which, e.g. Sorangium cellulosum So ce56 [25] have been sequenced. The overrepresentation of genes involved in secondary metabolism also explains the capability of myxobacteria to produce such a high number of potentially useful low molecular weight compounds. Over the past 25 years, more than 100 secondary metabolites with more than 450 structural variants have been isolated from myxobacteria at the HZI. Most of these compounds turned out to be new and show novel

unrelated structures as well as different biological activities with interesting mechanisms of action [24, 26, 27]. About a third of these myxobacterial compounds however did not show any biological or biochemical effect in our test battery, which until now predominantly focused at killing or inhibiting microbial growth. It should be pointed out that especially these compounds are of interest in exploring new targets. Here we DNA Damage inhibitor report on the efficacy of the secondary metabolite carolacton produced by S. cellulosum to biofilms of the cariogenic bacterium S. mutans. Figure 1 shows the structure of carolacton [28, 29], the elucidation of which as well as its production and isolation have been reported elsewhere [30]. Carolacton induced damage of S.