Influences of transtrans farnesol, a membranetargeting sesquiterpenoid, on Streptococcus mutans physiology and survival within mixedspecies oral biofilms

Trans-trans farnesol (tt-farnesol) is a bioactive sesquiterpene alcohol commonly found in propolis (a beehive product) and citrus fruits, which disrupts the ability of Streptococcus mutans (S. mutans) to form virulent biofilms. In this study, we investigated whether ttfarnesol affects cellmembrane function, acid production and/or acid tolerance by planktonic cells and biofilms of S. mutans UA159. Furthermore, the influence of the agent on S. mutans gene expression and ability to form biofilms in the presence of other oral bacteria (Streptococcus oralis (S. oralis) 35037 and Actinomyces naeslundii (A. naeslundii) 12104) was also examined. In general, tt-farnesol (1 mmol·L ^-1) significantly increased the membrane proton permeability and reduced glycolytic activity of S. mutans in the planktonic state and in biofilms (P<0.05). Moreover, topical applications of 1 mmol·L ^-1 ttfarnesol twice daily (1 min exposure/treatment) reduced biomass accumulation and prevented ecological shifts towards S. mutans dominance within mixedspecies biofilms after introduction of 1% sucrose. S. oralis (a noncariogenic organism) became the major species after treatments with tt-farnesol, whereas vehicletreated biofilms contained mostly S. mutans (>90% of total bacterial population). However, the agent did not affect significantly the expression of S. mutans genes involved in acidogenicity, acid tolerance or polysaccharide synthesis in the treated biofilms. Our data indicate that ttfarnesol may affect the competitiveness of S. mutans in a mixedspecies environment by primarily disrupting the membrane function and physiology of this bacterium. This naturally occurring terpenoid could be a potentially useful adjunctive agent to the current antibiofilm/anticaries chemotherapeutic strategies.