Influences of trans‐trans farnesol, a membrane‐targeting sesquiterpenoid, on Streptococcus mutans physiology and survival within mixed‐species oral biofilms

Jeon, Jongho; Pandit, Santosh; Xiao, Jin; Gregoire, Stacy; Falsetta, Megan L.; Klein, Marlise I.; Koo, Hyun

doi:10.4248/ijos11038

Cited by 60 publications

(57 citation statements)

References 32 publications

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“…The biofilm method used in this study was designed to mimic the formation of cariogenic biofilms according to the "ecological plaque" concept, as detailed previously (6,40,41). Briefly, hydroxyapatite discs (1.25 cm in diameter, surface area of 2.7 Ϯ 0.2 cm 2 ; Clarkson Chromatography Products, Inc., South Williamsport, PA) were coated with filtersterilized clarified human whole saliva (sHA) (6,40).…”

Section: Methodsmentioning

confidence: 99%

l -Arginine Modifies the Exopolysaccharide Matrix and Thwarts Streptococcus mutans Outgrowth within Mixed-Species Oral Biofilms

et al. 2016

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L-Arginine, a ubiquitous amino acid in human saliva, serves as a substrate for alkali production by arginolytic bacteria. Recently, exogenous L-arginine has been shown to enhance the alkalinogenic potential of oral biofilm and destabilize its microbial community, which might help control dental caries. However, L-arginine exposure may inflict additional changes in the biofilm milieu when bacteria are growing under cariogenic conditions. Here, we investigated how exogenous L-arginine modulates biofilm development using a mixed-species model containing both cariogenic (Streptococcus mutans) and arginolytic (Streptococcus gordonii) bacteria in the presence of sucrose. We observed that 1.5% (wt/vol) L-arginine (also a clinically effective concentration) exposure suppressed the outgrowth of S. mutans, favored S. gordonii dominance, and maintained Actinomyces naeslundii growth within biofilms (versus vehicle control). In parallel, topical L-arginine treatments substantially reduced the amounts of insoluble exopolysaccharides (EPS) by >3-fold, which significantly altered the three-dimensional (3D) architecture of the biofilm. Intriguingly, L-arginine repressed S. mutans genes associated with insoluble EPS (gtfB) and bacteriocin (SMU.150) production, while spxB expression (H 2 O 2 production) by S. gordonii increased sharply during biofilm development, which resulted in higher H 2 O 2 levels in arginine-treated biofilms. These modifications resulted in a markedly defective EPS matrix and areas devoid of any bacterial clusters (microcolonies) on the apatitic surface, while the in situ pH values at the biofilm-apatite interface were nearly one unit higher in arginine-treated biofilms (versus the vehicle control). Our data reveal new biological properties of L-arginine that impact biofilm matrix assembly and the dynamic microbial interactions associated with pathogenic biofilm development, indicating the multiaction potency of this promising biofilm disruptor. IMPORTANCEDental caries is one of the most prevalent and costly infectious diseases worldwide, caused by a biofilm formed on tooth surfaces. Novel strategies that compromise the ability of virulent species to assemble and maintain pathogenic biofilms could be an effective alternative to conventional antimicrobials that indiscriminately kill other oral species, including commensal bacteria. L-Arginine at 1.5% has been shown to be clinically effective in modulating cariogenic biofilms via alkali production by arginolytic bacteria. Using a mixed-species ecological model, we show new mechanisms by which L-arginine disrupts the process of biofilm matrix assembly and the dynamic microbial interactions that are associated with cariogenic biofilm development, without impacting the bacterial viability. These results may aid in the development of enhanced methods to control biofilms using L-arginine. Biofilms formed on surfaces are highly organized and structured microbial communities enmeshed in an extracellular matrix composed of polymeric substances, such as exopoly...

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Section: Methodsmentioning

confidence: 99%

l -Arginine Modifies the Exopolysaccharide Matrix and Thwarts Streptococcus mutans Outgrowth within Mixed-Species Oral Biofilms

et al. 2016

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“…Biofilms formed in the presence of farnesol contain less biomass, and display marked changes in matrix composition (13). Topical applications of farnesol reduce the biofilm matrix content (14). In addition to affecting the biofilm structure by reducing its biomass, farnesol seems to kill bacteria in biofilms, depending on the concentration (13).…”

Section: Introductionmentioning

confidence: 99%

Antibiofilm and Antibacterial Activities of Farnesol and Xylitol as Potential Endodontic Irrigants

et al. 2013

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This study investigated the antibiofilm and antibacterial effects of farnesol and xylitol in a series of experiments in order to evaluate their potential use as root canal irrigants. The following substances were tested: 0.2% farnesol; 5% and 20% xylitol; 0.2% farnesol plus 20% xylitol; and saline (control). For comparison with an established endodontic irrigant, 2.5% NaOCl was included in each test. Three experiments were conducted: the crystal violet assay, to evaluate the effects on the biofilm biomass; the dentin disinfection test, to evaluate the effects on bacterial viability in biofilms; and the root canal disinfection test, to simulate the use in the root canal environment. Farnesol was the most effective substance in reducing the biofilm biomass, followed by 20% xylitol. All substances affected bacterial viability in biofilms; farnesol showed the best results followed by the farnesol/ xylitol combination. Irrigation with all substances significantly reduced the bacterial load (p<0.001), but only the farnesol/xylitol combination was significantly more effective than saline (p=0.02). NaOCl was more effective than any other substance tested in the three experiments (p<0.001). The findings demonstrated that farnesol affected both the biofilm biomass and the viability of cells in the biofilm, while 20% xylitol affected only the biofilm biomass. Although not more effective than NaOCl, the combination of these two antibiofilm substances has potential to be used in endodontics in certain situations.

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“…In the present study, we tested a novel nonmicrobicidal approach, using selected naturally occurring food-derived agents (myricetin and tt-farnesol) that inhibit the ability of S. mutans to assemble biofilms, all without altering cell viability (19,21). Myricetin is an effective inhibitor of Gtf activity and also reduces expression of the gtfBC gene cluster, whereas tt-farnesol disrupts acid production, acid tolerance, and polysaccharide synthesis by affecting the permeability of the S. mutans membrane (19,20,26,28,29,31,32). Such properties may complement the cariostatic properties of fluoride by augmenting the overall biological activity against cariogenic biofilm formation while keeping its proven physicochemical effects (19,21).…”

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confidence: 99%

Novel Antibiofilm Chemotherapy Targets Exopolysaccharide Synthesis and Stress Tolerance in Streptococcus mutans To Modulate Virulence Expression In Vivo

Falsetta

Klein

Lemos

et al. 2012

Antimicrob Agents Chemother

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Fluoride is the mainstay of dental caries prevention, and yet current applications offer incomplete protection and may not effectively address the infectious character of the disease. Therefore, we evaluated the effectiveness of a novel combination therapy (CT; 2 mM myricetin, 4 mM tt-farnesol, 250 ppm of fluoride) that supplements fluoride with naturally occurring, food-derived, antibiofilm compounds. Treatment regimens simulating those experienced clinically (twice daily for <60 s) were used both in vitro over a saliva-coated hydroxyapatite biofilm model and in vivo with a rodent model of dental caries. The effectiveness of CT was evaluated based on the incidence and severity of carious lesions (compared to fluoride or vehicle control). We found that CT was superior to fluoride (positive control, P < 0.05); topical applications dramatically reduced caries development in SpragueDawley rats, all without altering the Streptococcus mutans or total populations within the plaque. We subsequently identified the underlying mechanisms through which applications of CT modulate biofilm virulence. CT targets expression of key Streptococcus mutans genes during biofilm formation in vitro and in vivo. These are associated with exopolysaccharide matrix synthesis (gtfB) and the ability to tolerate exogenous stress (e.g., sloA), which are essential for cariogenic biofilm assembly. We also identified a unique gene (SMU.940) that was severely repressed and may represent a potentially novel target; its inactivation disrupted exopolysaccharide accumulation and matrix development. Altogether, CT may be clinically more effective than current anticaries modalities, targeting expression of bacterial virulence associated with pathogenesis of the disease. These observations may have relevance for development of enhanced therapies against other biofilm-dependent infections.

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Influences of trans‐trans farnesol, a membrane‐targeting sesquiterpenoid, on Streptococcus mutans physiology and survival within mixed‐species oral biofilms

Cited by 60 publications

References 32 publications

l -Arginine Modifies the Exopolysaccharide Matrix and Thwarts Streptococcus mutans Outgrowth within Mixed-Species Oral Biofilms

l -Arginine Modifies the Exopolysaccharide Matrix and Thwarts Streptococcus mutans Outgrowth within Mixed-Species Oral Biofilms

Antibiofilm and Antibacterial Activities of Farnesol and Xylitol as Potential Endodontic Irrigants

Novel Antibiofilm Chemotherapy Targets Exopolysaccharide Synthesis and Stress Tolerance in Streptococcus mutans To Modulate Virulence Expression In Vivo

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