Biofilm Control Strategies in Dental Health - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 304

maturation in multispecies communities. The lux S gene, responsible for the expres-
sion of AI-2, is conserved among many species of bacteria, including S. mutans ,
S. gordonii , Streptococcus oralis , P. gingivalis , A. actinomycetemcomitans , and
other oral microorganisms (Frias et al. 2001 ; Jakubovics 2010 ).
The species-specific QS autoinducers N -acyl homoserine lactones (autoinducer-1)
have not been identified in oral bacteria (Jakubovics and Kolenbrander 2010 ).
However, many oral microorganisms produce and/or respond to the interspecies
signal AI-2. AI-2 is the collective term given to a number of molecules that
spontaneously form an equilibrium when 4,5-dihydroxy-2,3-pentanedione (DPD)
is dissolved in water. Bacteria produce AI-2 during amino acid metabolism as a
product of the enzyme encoded by the luxS gene. AI-2 plays an important role in
regulating the essential activities of oral pathogens. AI-2 QS regulates iron acqui-
sition in the periodontal pathogens P. gingivalis and A. actinomycetemcomitans
(Shao and Demuth 2010 ) and modulates protease and haemagglutinin activities in
P. gingivalis (Burgess et al. 2002 ). Additionally, AI-2 also regulates biofilm
formation in oral pathogens . A. actinomycetemcomitans lux S mutants are capable
of forming a mature biofilm, but they exhibit significantly lower total biomass and
biofilm depth when compared with the wild-type strain (Shao and Demuth 2010 ).
Similarly, lux S mutants of S. mutans form a defective biofilm compared to wild
type due to a decrease in glycosyltransferase activity, suggesting that the activity of
this enzyme is controlled by AI-2 (Huang et al. 2009 ; Yoshida et al. 2005 ).
QS inhibitors have the potential to control biofilm growth and maturation with
the advantage of reducing the generation of mutants resistant to the treatment. The
increasing interest in interfering with these signaling systems as a way of control-
ling biofilms (Quorum Quenching) is reflected by the increasing number of patents
filed using this approach (more than 45 since 2009) (Romero et al. 2012 ).
Recently, it was shown that two QS inhibitors (5 Z )-4-bromo-5-
(bromomethylene)-2(5H)-furanone (furanone compound) and D -ribose inhibited
dual biofilm formation between Fusobacterium nucleatum and members of the
“red complex” ( Porphyromonas gingivalis , Treponema denticola , and Tannerella
forsythia ) (Jang et al. 2013 ). Fusobacterium nucleatum is the major coaggregation
bridge organism that links early colonizing commensals and late pathogenic colo-
nizers in dental biofilms via the accretion of periodontopathogens from the “red
complex.” Disturbance of coaggregation and biofilm formation between these
organisms may have an impact in controlling pathogenic biofilm. He and collabo-
rators have shown that by using the synthetic QS inhibitor furanone C-30, biofilm
formation by Streptococcus mutans was significantly reduced (He et al. 2012 ).
Although there are no reports that suggest production of AHLs by P. gingivalis ,it
has been shown that synthetic N -acyl HSL analogues can inhibit biofilm formation
by this organism (Asahi et al. 2010 ). The mechanisms by which these analogues
interfere with biofilm formation in P. gingivalis are still unknown.
Although S. mutans possesses the AI-2 system (Merritt et al. 2003 ), its primary
QS system is comprised of the Competence Stimulating Peptide (CSP) and the
ComD/ComE two-component signal transduction system. In addition to biofilm
formation, the CSP-mediated QS system in S. mutans also affects its acidogenicity,