Oral streptococci aggregated by gp340 are cleared from the host before they have the opportunity to adhere to the pellicle of the tooth, thus disrupting an integral part of the adhesion process; protein components of mucus also exhibit similar properties (Golub et al., 1985; Courtney & Hasty, 1991). Flavonols have a similar effect, and galangin has been shown to induce aggregation of Gram-positive bacteria (Cushnie et al., 2007). It has Vorinostat cell line been suggested that flavonols target the bacterial cytoplasmic membranes causing membrane fusion between microorganisms, resulting in leakage of intra-membranous

materials which promotes aggregation (Cushnie et al., 2007). Rapid bacterial aggregation enables the host’s defences to remove potential pathogens

(Lamont & Rosan, 1990), resulting in a marked reduction in bacterial numbers. Research has demonstrated that large aggregate clumps are more easily detected by the innate immune system compared to those bacteria in biofilm or planktonic form (Ligtenberg et al., 1990; Kitada & Oho, 2010). Therefore, it is possible that flavonols could be used to prevent bacterial adhesion in the human host as a novel anti-adhesive compound, by virtue of its ability to promote aggregation and potentially facilitate bacterial clearance (Koop et al., 1989; Courtney & Hasty, 1991). Bacterial aggregation and biofilm development are intimately related. The mature biofilm is comprised of numerous ordered aggregates of bacterial cells. In this study, it is evident that morin impeded biofilm development, resulting in a 50% reduction in biomass using concentrations of 225 μM BYL719 mouse and above. It likely that the rapid aggregation mediated by morin meant that instead of being freely available to attach and colonize the MTP, bacteria adhered to

one another. This supports recent research showing that rapid aggregation can influence biofilm formation (Ahn PIK3C2G et al., 2008). Flavonols are known to disrupt the development of biofilms of Candida albicans, P. aeruginosa and S. mutans despite the precise mechanisms remaining unknown (Jayaraman et al., 2010). Recent data have also indicated that flavonols have an impact at the gene regulatory level, specifically reducing the expression of sortase enzymes that are required to anchor surface proteins into the bacterial cell wall (Kang et al., 2006; Hirooka et al., 2009). It is possible that in addition to the aggregation effect that may impede biofilm development, that surface proteins involved in adhesion may not be properly processed or in fact present on the bacterial cell surface, which could reduce the likelihood of bacterial adhesion. Therefore, it seems likely that the effects observed in this study are the consequence of multifactorial mechanisms mediated by morin. Further studies will help to ascertain the potential for morin to be used in topical treatments, for example, for skin and wound infections. The authors thank Howard Jenkinson for providing S.