COBIOT-939; NO.

OF PAGES 8

Available online at www.sciencedirect.com

Functional foods and strategies contrasting bacterial adhesion

Caterina Signoretto1, Pietro Canepari1, Monica Stauder2,
Luigi Vezzulli2 and Carla Pruzzo2
Antibacterial strategies targeting bacterial adhesion to
substrates are considered a valuable alternative to traditional
antibiotic therapy, in view of the great advantage they bring
in combating the infectious process at the very early stage
without selecting for drug resistant cells. Amongst bioactive
compounds with activity against bacterial adhesion, several
are found in natural food and beverages, such as cranberry,
tea, coffee, wine and milk. For the analysis of their antiinfective potential, successful experimental models can be
conducted using different substrates from the oral cavity.
Studies conducted so far in this field allowed the discovery of
a variety of anti-adhesive fractions and compounds proven
to be effective against bacterial traits involved in the
development of oral pathologies such as caries and
gingivitis/periodontitis. Discovering new anti-adhesive
compounds from natural products, unravelling and testing
their prophylactic and therapeutic values, and improving
their use in the general population are promising new
frontiers in the global fight against human infectious
diseases.

Natural food and beverages, which are known to contain a

variety of bioactive substances, could be very useful for
the selection of compounds with anti-virulence properties. Furthermore, the oral cavity, whose environment is
conditioned by the diet, can be considered as an excellent
model system for exploring the anti-infective potential of
foodstuff components [2]. Amongst virulence properties
of pathogenic oral bacteria (e.g. Streptococcus mutans, Porphyromonas gingivalis), adhesion to tooth and gingival
surfaces, being a prerequisite for the formation of dental
plaque and induction of damage to the host, is an ideal
target of new anti-infective agents [3].

Addresses
1
Dipartimento di Patologia e Diagnostica, Sezione di Microbiologia,
Universita` di Verona, Strada Le Grazie 8, 37134 Verona, Italy
2
Department for the Study of Territory and its Resources, University of
Genoa, Corso Europa 26, 16132 Genova, Italy

Bacterial adhesion and anti-adhesion

strategies

Corresponding author: Pruzzo, Carla (carla.pruzzo@unige.it)

Current Opinion in Biotechnology 2011, 23:18

This review comes from a themed issue on
Food biotechnology
Edited by Gabriella Gazzani and Michael Grusak

0958-1669/$ see front matter

# 2011 Elsevier Ltd. All rights reserved.
DOI 10.1016/j.copbio.2011.08.006

Introduction
The evolution, selection and spread of bacterial resistance to a wide range of antibiotics make the development
of novel strategies to prevent and treat bacterial infections
crucial. The search for agents targeting bacterial virulence
properties (e.g. adhesion, colonization, invasion, production of toxins) is considered a valuable alternative
strategy to antibiotic therapy, having the great advantage
of combating the infectious process without selecting for
drug resistant cells, and not causing deleterious effects on
host microbiota [1].
www.sciencedirect.com

In this article, after a brief description of the main antiadhesion strategies that are subjects of ongoing studies, a
review is given on recent literature dealing with food/
beverage types and active components known to affect
adhesive properties of bacteria involved in caries and
periodontal diseases.

Firm adhesion of bacteria to human surfaces is mediated

by specific interactions occurring between bacterial surface structures (adhesins) and complementary receptors
located on either the targeted substrate or the conditioning layer covering it. Adhesion may also involve hydrophobic and other non-specific interactions, these being
mainly implicated in the initial reversible phase of the
process. Adhesion offers bacteria several advantages including resistance to host cleansing mechanisms, access
to nutrients, colonization of the surface, delivery of toxic
agents close to their target, and, in some cases, entry into
epithelial cells [4]. In general, adhesins recognize specific
receptors and molecular conformations [3,5], the target
specificity being helpful in guiding the bacterium to the
site that can support its growth [5]. Bacteria may carry
adhesins for more than one target surface and may employ
more than one adhesin for binding a substrate; multiple
adhesins can act in a concerted way and can be expressed
at different stages during infection [3,4]. Bacteria can
also display specific ligands and/or receptors for other cell
types; as a result of cell-to-cell recognition, a network of
interacting (co-aggregated) bacteria is formed [6].
Both adhesion and co-aggregation are crucial for the
development of complex multispecies biofilms in diverse
habitats. Many clinical infections are ascribed to biofilms,
and many persistent, chronic or recurrent bacterial infections are linked to biofilm formation. Some examples are
Current Opinion in Biotechnology 2011, 23:18

Please cite this article in press as: Signoretto C, et al. Functional foods and strategies contrasting bacterial adhesion, Curr Opin Biotechnol (2011), doi:10.1016/j.copbio.2011.08.006

COBIOT-939; NO. OF PAGES 8

2 Food biotechnology

pulmonary infections in patients with cystic fibrosis,

dental plaques and gingivitis, the last two being dependent on the formation of the specific biofilm named dental
plaque. It is well known that bacteria growing in biofilms
are physiologically distinct from bacteria growing in a
planktonic state [7]. One of the most investigated
properties of biofilm-grown bacteria is their increased
antimicrobial resistance [8]. The fact that bacteria that
are inherently susceptible to antibiotics can exhibit multidrug tolerance when included in a biofilm, in addition to
their notable tendency to acquire mobile resistance
genes, represents a further problem in the treatment of
biofilm-associated infectious diseases [9].
Targeting bacterial virulence is a very interesting option
to antimicrobial therapy offering a number of chances to
prevent/block the infectious process and to abolish/
reduce tissue damage [1]. In this frame, recent efforts
towards anti-virulence therapy include the use of compounds that interfere with the first step of infection, that
is adhesion to host tissues [3]. Several strategies have
been considered to impair bacterial adhesion (Figure 1)
including: coating the target substrate [5,10,11], affect-

Figure 1

(a) adhesion (b) coating of the

(c) inhibition of

target surface

adhesin
biosynthesis

(e) adhesin
analogs

(f) receptor
analogs

(d) inhibition of
receptor
glycosylation

(g) anti-adhesin
antibodies

bacterial adhesin

targeted substrate receptor

bacterial cell

targeted substrate
Current Opinion in Biotechnology

Strategies to inhibit bacterial adhesion. (a) Control: a bacterial cell

adhering to the targeted substrate. (b) Coating of the targeted substrate.
(c) Inhibition of adhesin biosynthesis and/or anchoring to the
peptidoglycan. (d) Inhibition of glycosylation of the receptor on the
targeted substrate. (e) Use of adhesin analogues that bind the receptor
of the targeted substrate. (f) Use of receptor analogues that bind
bacterial adhesins. (g) Use of antibodies against bacterial adhesin.
Current Opinion in Biotechnology 2011, 23:18

ing adhesin biosynthesis [3] and surface anchoring [12],

affecting glycosylation of the targeted substrate [13,14],
using either adhesin analogues [5,15], or receptor
analogues [16,17] or anti-adhesin antibodies [18]. In general, the presence of multiple bacterial adhesins, the
variability of the adhesin domain that binds the receptor,
and the lack of appropriate methods to deliver the
adhesion inhibitors to their site of action are major
obstacles to anti-adhesion therapy. Further problems
are the possible low affinity of free receptors to the
bacterial ligands, as in the case of the approach based
on receptor analogues, and the presence in the adhesin of
common epitopes with human proteins, as in the case of
immunization against bacterial adhesin. The use of cocktails of inhibitors directed towards different adhesins, a
better knowledge of the properties of both adhesins and
targeted receptors, together with an improvement of
technologies for isolating and producing inhibitors in high
purity and high amount may help to overcome these
problems.

Dental plaque and oral pathogenic bacteria

The resident oral microbiota consists of a highly heterogeneous population in which bacteria are predominant
and cohabit in a fragile balance with the host. Dental
plaque is defined as a bacterial biofilm enveloped by, and
tightly adherent to the tooth surface via exopolysaccharides (EPSs) of bacterial origin [19]. In addition to suboptimal daily oral hygiene, several factors may promote
abnormal growth of the dental plaque including host
factors and diet. The main oral pathologies resulting from
plaque accumulation are caries and gingivitis/periodontitis, both being diffused worldwide and included amongst
the most prevalent and costly infectious diseases. Human
caries is an acid demineralization of teeth caused by
bacteria belonging to the normal oral microbiota (S.
mutans and Streptococcus sobrinus) in the presence of
sucrose, the sugar worldwide used as sweetener. The
carious process is conventionally subdivided into three
phases: in the initial, sucrose-independent stage, odontopathogenic bacteria bind the salivary glycoproteins
located on the tooth surface. Interaction is allowed by
the presence of bivalent cations such as Ca2+ and a variety
of bacterial adhesins. The second stage is dependent on
the production of glucans from sucrose by the activity of
distinct S. mutans glucosyl transferases (GTFs) acting
sequentially to synthesize a final, very hydrophobic glucan called mutan, which is tightly adherent to the tooth
surface [20]. Bacterial mutan-binding ligands are
involved in the process. During the third phase, S. mutans
produces lactic acid, responsible for enamel demineralization and caries lesion development. Gingivitis and
periodontal diseases are the main cause of dental loss
in adults. As opposed to dental caries in which an odontopathogenic species predominate, aetiology of gingivitis
and periodontitis is more complex and, together with host
factors, a bacterial consortium, mainly composed of strict
www.sciencedirect.com

Please cite this article in press as: Signoretto C, et al. Functional foods and strategies contrasting bacterial adhesion, Curr Opin Biotechnol (2011), doi:10.1016/j.copbio.2011.08.006

COBIOT-939; NO. OF PAGES 8

Bacterial adhesion and functional foods Signoretto et al.

anaerobes, is implicated as the trigger. After colonization

and multiplication at subgingival sites, a mix of bacterial
toxins produced by the consortium is responsible for the
tissue damage resulting in gum detachment from teeth
and production of the characteristic periodontal pockets,
whose depth and severity increase with the progression of
the disease. Clinical and laboratory studies have shown
that, for dental and gum pathologies, plaque removal by
various means (both professional and domiciliary
hygiene) and lowering bacterial counts reduce or stop
the disease progression.

Foodstuff with anti-adhesion potential for oral

care
From approximately the early 1980s there has been an
increasing interest in natural biologically active compounds with potential therapeutic uses in medicine. Folk
medicine around the world has used herbs, plants and
derived food and beverages over thousands of years to
cure human diseases and maintain oral hygiene. Even
with the advent of modern medicine, many products from
plants have been utilised as the basis for the development
of new pharmaceuticals. Oral hygiene has represented a
useful target for plant-derived chemicals and this is skilfully supported by the observation that populations that
regularly consume foods and beverages containing biologically active components have a better oral health
[21]. Worthy of mention is the Japanese popular notion
that green tea makes the mouth clean and there is an old
tradition that those who drink large amounts of tea have
less tooth decay. In support of this popular notion, very
recently, it has been shown that long-standing drinking
habits (regular and moderate consumption of coffee or
red wine versus water) are associated with changes in
dental plaque microbial community, and the presence of
a microbiota normally associated with good oral health
[22]. The vast majority of these bioactive phytochemicals are included in the broader family of polyphenols.
Polyphenols are widespread groups of substances produced by plants and, due to their anti-oxidant activity,
have long been known to be endowed with a broad range
of health-associated effects [23]. Both in vitro and in vivo
studies have demonstrated that polyphenols are capable
of selectively interfering with virulence traits of odontopathogenic and periodontopathogenic bacteria. Amongst
the various proposed activities, several food and beverage components have been shown to possess anti-plaque
activity as a result of their ability to interact with bacterial
adhesion and co-aggregation [23]. Table 1 shows a list of
representative foods and beverages active against S.
mutans and/or periodontopathogenic anaerobes. In most
cases, the active fractions/compounds modify the bacterial surface and/or mask targeted substrate receptors.
However, the bioactive components are not always
exactly identified and, in several cases, the precise
mechanism of action is unclear and/or not deeply investigated yet.
www.sciencedirect.com

Tea

Three different kinds of tea are commercially available:

green, black and oolong tea. All originate from leaves of
Camellia sinensis but result from different treatments:
drying fresh tea leaves, fermenting tea leaves or partial
oxidation of tea leaves, respectively. Remarkable differences in chemical concentrations result in the three
different types of tea. Green tea is endowed with the
highest polyphenols concentrations, being up to 30% of
the dry weight, and include flavonols (mainly catechins,
molecular mass <459 Da), flavonoids and phenolic acids.
Alkaloids such as caffeine, theobromine and theophylline
account for an additional 4%. A cup of green tea contains
about 300 mg of catechins. Black tea is the result of
oxidation and condensation of catechins during the fermentation process to produce dark-coloured molecules of
5001000 Da which represent about 2030% of the dry
weight. Oolong tea contains a mixture of the abovementioned molecules, being an intermediate between
green and black tea. The salutary effects of the tea drink
were recognized thousands of years ago, and tea was the
first to be included in the group of beverages endowed
with functional properties. The scientific approach to
prove the effect of tea on oral health dates back to the
early 1950s but the specific role of tea polyphenols was
determined in the 1980s. Experimental evidence that
green tea catechins prevent the adhesion of S. mutans
to saliva-coated hydroxyapatite (HA) discs has been provided by Otake et al. [24]. The inhibition of the adhesion
has been attributed to modification of the bacteria,
possibly via changes in the conformation of bacterial
surface molecules. Moreover, tea catechins adsorbed to
the dental acquired pellicle modify their structural properties and prevent further binding capability [25]. In
addition to the reduced adhesion capability of S. mutans
to HA discs, Otake et al. [24] showed inhibition of GTF
activity in vitro by green tea catechins. Inhibitory effects
due to a high molecular weight compound extracted from
the partially fermented oolong tea were shown by Nakahara et al. [26] on S. sobrinus GTF activity. Inhibition of
GTF activity has been attributed to binding of the
polymeric polyphenol fraction to the glucan-binding
domain region of the enzyme.
The effects of tea have also been evaluated on periodontopathogenic bacteria such as P. gingivalis and Prevotella
intermedia. Inhibition of the adhesion of P. gingivalis to
buccal epithelial cells was determined for specific individual green tea catechins (e.g. epigallocatechin-3-gallate) [27]. In addition, the same tea compounds were
proved active against toxic end metabolites of P. gingivalis
[28] and P. intermedia tyrosine phosphatase [29].
Cranberry

Cranberry (Vaccinium macrocarpon) juice and fruits are

reported as health foods endowed with potential antioxidant and anti-cancer activities with vasorelaxing
Current Opinion in Biotechnology 2011, 23:18

Please cite this article in press as: Signoretto C, et al. Functional foods and strategies contrasting bacterial adhesion, Curr Opin Biotechnol (2011), doi:10.1016/j.copbio.2011.08.006

Source

Chemical compound

In vitro activity (hypothesized mechanism of action)

Targeted bacteria

Tea (Camellia sinensis)

Flavonols: catechins (<450 Da)

Anti-adhesion (bacterial surface modification,

modification of acquired pellicle structural
properties, binding to GTF glucan-binding domain)
Anti-adhesion

P. intermedia, P. gingivalis

[28,29]

Cranberries (Vaccinium
macrocarpon)

NDM, flavonols, anthocyanins,

proanthocyanidins

Anti-adhesion, increase of detachment of

biofilm, inhibition of co-aggregation
(bacterial surface modification)
Antibiofilm (inhibition of GTFs and mutan synthesis)
Inhibition attachment to mammalian cells
(cell surface modifications)
Inhibition of mixed biofilm formation (bacterial
surface modification and inhibition of
bacterial co-aggregation)

S. mutans

[30]

P. gingivalis

[48]

P. gingivalis + F. nucleatum

[49]

Anti-adhesion (inhibition of mutan synthesis,

inhibition of GTFs)
Antibiofilm
Anti-adhesion, increase of detachment of adherent
bacteria, inhibition of co-aggregation
Antibiofilm (cell division alteration following DNA
synthesis inhibition)

S. mutans

[50]

P. gingivalis, P. intermedia
S. mutans

[50]
This paper

P. intermedia

[38,47]

Crude water extracts from both

green and roasted coffee beans
LMM fraction (<3500 Da) (natural
and roasting induced compounds)
HMM fraction (>3500 Da) (melanoidin
and non-melanoidin compounds)

Anti-adhesion (coating of dental surface and

inhibition of interactions with bacteria)
Anti-adhesion (coating of dental surface and
inhibition of interactions with bacteria)
Anti-adhesion, antibiofilm, increase of detachment
of adherent bacteria

S. mutans

[31]

S. mutans

[32]

S. mutans

[32]

Crude water extracts from roasted beans

Anti-adhesion, increase of detachment of adherent

bacteria (masking of saliva-coated HA receptors,
and/or modification of bacterial adhesins)
Anti-adhesion (masking of saliva-coated HA
receptors and/or modification of bacterial adhesins)
Anti-adhesion (masking of saliva-coated HA receptors
and/or modification of bacterial adhesins)
Antibiofilm

S. mutans and other oral

streptococci

[33]

S.
S.
S.
S.
S.

[33]

Anti-adhesion, (masking of saliva-coated HA receptors

and/or modification of bacterial adhesins), increase of
detachment of adherent bacteria
Anti-adhesion, antibiofilm
Anti-adhesion (inhibition of GTFs)

S. mutans

[35]

S. mutans
S. mutans

[35]
[36]

Anti-adhesion (coating of salivary pellicle)

S. mutans

[3942]

Favouring adhesion of less or non cariogenic bacteria

A. naeslundii

Edible mushroom
(Lentinus edodes)

Solvent extract fractions

LMM aqueous fraction (<5000 Da)

Coffee (Coffea arabica)

Barley coffee
(Hordeum vulgare)

LMM fraction (<1000 Da) (polyphenols,

zinc and fluoride ions)
HMM fraction (>300,000 Da)

Wine and grapes

(Vitis vinifera)

Dealcoholized red wine

www.sciencedirect.com

Proanthocyanidins, red pigments

Grapes and pomace
Milk

Proteins (e.g. caseins, lactoferrin,

lactoalbumin)

NDM = non-dialyzable material; LMM = low molecular mass; HMM = high molecular mass.

S. mutans

References

mutans, S. intermedius,
constellaturs
mutans, S. intermedius,
constellatus
mutans

[24,26]

[33]
[34]

COBIOT-939; NO. OF PAGES 8

Representative examples of natural food and beverages and their main components inhibiting bacterial adhesive properties in the oral cavity.

4 Food biotechnology

Current Opinion in Biotechnology 2011, 23:18

Please cite this article in press as: Signoretto C, et al. Functional foods and strategies contrasting bacterial adhesion, Curr Opin Biotechnol (2011), doi:10.1016/j.copbio.2011.08.006

Table 1

COBIOT-939; NO. OF PAGES 8

Bacterial adhesion and functional foods Signoretto et al.

effects as well as inhibitory effect on bacterial adhesion in

urinary tract and biofilm formation [29]. Total polyphenols amount to 1012% of the dry weight. Several biological activities have been attributed to non-dialyzable
material (NDM) of a high molecular mass cranberry
fraction. Details of the activity of cranberry components
against infectious agents are not described, being given
elsewhere in this issue [30].
Coffee and barley coffee

Like tea, coffee brews are widely consumed. Coffee

beverages are very complex mixtures of several hundred
chemicals that either occur naturally or are induced by the
roasting process in the form of nicotinic acid or melanoidins. Beverages obtained from both green and roasted
beans have been tested for their ability to inhibit S.
mutans sucrose-independent absorption to saliva-coated
HA at sub-inhibitory concentrations. Inhibition of S.
mutans adhesion to HA was observed both when coffee
was present in the absorption mixture and when it was
used to pre-treat HA suggesting that the coffee active
molecule(s) may adsorb to the dental surfaces hampering
bacterial interactions with dental enamel and/or glycoproteins of the acquired pellicle [31]. Several compounds
present in coffee beverages are responsible for the
observed anti-adhesion activity and include small compounds naturally present in coffee beans (chlorogenic
acid and trigonelline) as well as others induced by roasting
(nicotinic acid and melanoidins). More recently, coffees
capability to reduce S. mutans sucrose-dependent
adhesion to HA and biofilm formation as well as capability
to increase bacterial detachment from the beads was also
ascribed to high molecular mass melanoidin and nonmelanoidin components [32].
Barley coffee is a beverage produced with roasted barley
beans and is generally considered a coffee substitute.
Inhibition of sucrose-dependent and sucrose-independent adhesion to HA of S. mutans and other oral streptococci, as well as an increase in their detachment from
preformed biofilm were observed for barley coffee concentrations devoid of antimicrobial activity. The
<1000 Da molecular mass fraction, which contains polyphenols, zinc and fluoride ions, and the >300,000 Da MM
fraction, which consists of a strong brown anti-oxidant,
melanoidin, both displayed anti-adhesive properties
towards S. mutans, Streptococcus intermedius and Streptococcus constellatus. High-MM melanoidin was not detected in
unroasted barley, indicating that it forms during the
roasting process [33,34]. The effects seem to depend
on masking of saliva-coated HA receptors for bacterial
ligands as well as on masking and/or modification of
bacterial adhesins.

the rich content of polyphenols in grapes and, especially,

in their solid materials such as seeds, skin and stems.
Inhibition of S. mutans sucrose-dependent and sucroseindependent adhesion to HA and biofilm formation, as
well as an increase in bacterial detachment from HA were
detected in dealcoholized red wine. The inhibitory
activity was associated to proanthocyanidins and, albeit
to a lower extent, red pigments [35]. The effects were
observed at concentrations devoid of antibacterial activity
and might be ascribed to the masking of saliva treated HA
receptors for microbial ligands as well as to the masking
and/or modification of bacterial adhesins.
Timothe et al. [36] have tested polyphenols extracted
from grapes and pomace (a waste product of the wine
making) on a number of virulence factors of S. mutans.
All the types of grapes and pomace, although with
different polyphenol concentrations, proved capable
of inhibiting S. mutans GTFs, that is the bacterial
enzymes involved in EPS production and biofilm
growth. This last result is intriguing as waste products,
such as pomace, could prove to be useful either as an
economic source of polyphenols for medical applications
or as functional food ingredients.
Mushroom

Lentinus edodes (shiitake, an edible mushroom very popular in Japan) contains components endowed with inhibitory effects on water-insoluble glucan formation from
sucrose by crude GTFs of both S. mutans and S. sobrinus,
as well as an anti-plaque activity [37]. Very recently,
shiitake mushroom aqueous extract has been proved to
inhibit S. mutans adhesion to HA and biofilm formation, as
well as co-aggregation between pairs of Fusobacterium
nucleatum and S. mutans, and F. nucleatum and Neisseria
subflava (Stauder et al.: Abstract P1154, 21st ECCMID/
27th ICC, Milan, Italy, May 2011). Most of the inhibitory
activity was retained in the low molecular mass fraction
(<5000 Da) obtained by ultrafiltration of the aqueous
extract.
Furthermore, analysis of the mode of action and the
morphogenetic effects of this mixture of compounds in
P. intermedia has shown that DNA synthesis is the main
target in bacteria and, as a result of this, septum formation
inhibition occurs with subsequent cell elongation, thus
suggesting an antibiotic-like activity [38]. This statement
has been further supported by the observation that subinhibitory concentrations displayed morphogenetic
effects such as those induced by doses equal to or higher
than the minimal inhibitory concentration, as previously
demonstrated for both b-lactams and quinolones.
Milk

Wine and grapes

Several studies have suggested that moderate wine consumption has a beneficial effect on human health due to
www.sciencedirect.com

Milk is an excellent protein food for humans and animals

of all ages. The natural virtues of milk in protecting
mammals against numerous pathogenic bacteria have
Current Opinion in Biotechnology 2011, 23:18

Please cite this article in press as: Signoretto C, et al. Functional foods and strategies contrasting bacterial adhesion, Curr Opin Biotechnol (2011), doi:10.1016/j.copbio.2011.08.006

COBIOT-939; NO. OF PAGES 8

6 Food biotechnology

been known for many years. Milk also contains factors

that have anti-cariogenic properties and, in the late 1950s,
dairy products were recognized as foods that are effective
in preventing dental caries [39,40]. Milk proteins, such as
bovine and human caseins and lactoferrin, inhibit initial
attachment of cariogenic mutans streptococci to HA
coated with saliva or purified saliva host ligands [40].
Early studies showed that incorporation of caseinoglycomacropeptide and caseinophosphopeptide into the salivary pellicle inhibits adherence of mutans streptococci
and causes an ecological shift which is linked to their
observed modified cariogenic potential [41]. Recently,
avid inhibition towards S. mutans adherence to salivacoated or gp340 (a salivary scavenger protein endowed
with bacterial recognition properties)-coated HA was
shown for caseins, lactoferrin, IgA and IgG, and moderate
inhibition for alpha-lactalbumin and bile salt-stimulated
lipase [42]. The inhibitory epitopes of beta-casein and
lactoferrin were delineated by the use of synthetic peptides. In contrast, both bovine and human milk coated on
HA promotes attachment of Actinomyces naeslundii and
other streptococci in vitro, thus suggesting the shift
towards a less cariogenic oral microbiota [40].

allows reduction of both plaque and gingival indices

[47]. Despite the limited investigations in vivo, ongoing
studies clearly indicate that natural foods and beverages
are an important and still underestimated source of
novel and effective anti-caries and anti-plaque compounds. Additional clinical studies are needed to prove
the real efficacy and safety of these new promising
compounds.

Honey

The ways by which the use of foodstuff active components could be improved may be diverse, for example
simply suggesting an increase of beneficial food and
beverage consumption, producing functional foods and
genetically modified plants with increased contents of
naturally occurring healthcare components, or incorporating active compounds in cosmetic products for daily oral
hygiene. These approaches would contribute to overcome the increasing mistrust of man-made chemicals
that has been reported amongst the general public, properly responding to the emerging need for natural occurring compounds. Several tasks, however, should be
addressed in the near future in order to obtain a safe
and successful application of these substances. These
include: first, identification of active food compound(s)
at the molecular level; second, understanding of factors
and conditions affecting their biological activity; third,
definition of the suitable oral delivery systems; fourth,
toxicological studies; and, last but not the least, fifth, large
scale validation in clinical trials.

Honey has been used since ancient times in folk medicine against infectious diseases and wound healing.
Because of the high carbohydrate content, honey exerts
anti-adhesion activity comparable to that of human milk,
as evaluated against Pseudomonas aeruginosa [17]. A number of studies showed its antibacterial effect on oral
bacteria and a pilot study conducted with a chewable
honey leather reported its potential therapeutic role in
the treatment of gingivitis and periodontal disease [43].
Recently, manuka honeys weakly inhibited S. mutans
adherence to a glass surface at sub-inhibitory concentrations, whilst exerting strong antibiofilm activity at
concentrations equal to or higher than the minimal inhibitory concentration [44].

In vivo and clinical studies

Despite several studies performed in vitro to assess the
anti-adhesion activity of natural compounds, only a few
studies have been conducted in vivo by using the rodent
model of dental caries, and even less have been conducted at the clinical level. For example, studies have
shown that green or oolong tea extracts significantly
reduce plaque accumulation and the number of caries
lesions in rats [45]. Epidemiological studies performed
in different populations have shown that tea drinkers
have better values of parameters connected to good oral
health. Reduction of dental plaque deposition in
humans has been obtained with oolong tea extract
[46]. A clinical study has shown that a mouthwash
based on a cranberry extract reduces significantly the
salivary S. mutans counts [30] and, very recently, a
mouthwash composed of shiitake mushroom extract
Current Opinion in Biotechnology 2011, 23:18

Conclusions
A substantial number of scientific reports describing in
vitro antimicrobial activity of components of widely consumed natural foods and beverages provide evidence of
their usefulness in maintaining oral health. The therapeutic and prophylactic value of such compounds is
greatly supported by the fact that, in several cases (as
reported in this paper for the oral cavity), their antiinfective potential relies on the inhibition of bacterial
adhesion at the mucosal level. Acting at the beginning of
the infectious process, these compounds can exert their
activity before bacteria are embedded in a biofilm and
become less sensitive to any therapeutic agents, both
natural and man made.

In a general perspective, these studies reverse the common perception of food effects on oral microbiota and
health, in that foods/food components are no longer
deleterious (e.g. sucrose and dental caries) but, possibly,
beneficial for disease prevention and therapy.

Acknowledgements
The help by Dr Mariapaola Moreno with the figure presentation is greatly
acknowledged.
This study was supported by the European Community Research Project
Nutrident, contract No. FOOD-CT-2006-036210, and Ministero
dellIstruzione, dellUniversita` e della Ricerca (PRIN grant 2009), Italy.
www.sciencedirect.com

Please cite this article in press as: Signoretto C, et al. Functional foods and strategies contrasting bacterial adhesion, Curr Opin Biotechnol (2011), doi:10.1016/j.copbio.2011.08.006

COBIOT-939; NO. OF PAGES 8

Bacterial adhesion and functional foods Signoretto et al.

References and recommended reading

Papers of particular interest, published within the period of review,
have been highlighted as:
 of special interest
 of outstanding interest
1.


Cegelski L, Marshall GR, Eldridge GR, Hultgren SJ: The biology

and future prospects of antivirulence therapies. Nat Rev
Microbiol 2008, 6:17-27.
This article reviews up-to-date knowledge on new available strategies
targeting bacterial virulence as an alternative approach to antimicrobial
therapy representing a new paradigm to empower the clinician to prevent
and treat infectious diseases.

2.


Jeon J-G, Rosalen PL, Falsetta ML, Koo H: Natural products in

caries research: current (limited) knowledge, challenges and
future perspective. Caries Res 2011, 45:243-263.
This recent review article critically evaluates the current knowledge of
natural compounds with potential in anti-caries chemotherapy. Of particular interest is the detailed model suggested by the authors for investigating the use of natural products in caries research.

3.


Ofek I, Hasty DL, Sharon N: Anti-adhesion therapy of bacterial

diseases: prospects and problems. FEMS Immunol Med
Microbiol 2003, 38:181-191.
In this article authors provide an extensive review of various approaches
to anti-adhesion therapy, including the use of receptor and adhesin
analogues, dietary constituents, sublethal concentrations of antibiotics
and adhesin-based vaccines all serving as new means to fight infectious
diseases.
4.

Ofek I, Doyle RJ: Common themes in bacterial adhesion. In

Bacterial Adhesion to Cells and Tissues. Edited by Ofek I, Doyle RJ.
New York: Chapman and Hall; 1994:513-562.

5. Klemm P, Munk Vejborg R, Hancock V: Prevention of bacterial


adhesion. Appl Microbiol Biotechnol 2010, 88:451-459.
This is an updated and well-documented description of different techniques so far developed to inhibit bacterial adhesion.
6.

Rickard AH, Gilbert P, High NJ, Kolenbrander PE, Handley PS:

Bacterial coaggregation: an integral process in the development
of multi-species biofilms. Trends Microbiol 2003, 11:94-100.

7. Stewart PS, Franklin MJ: Physiological heterogeneity in

 biofilms. Nat Rev Microbiol 2008, 6:199-210.
This review is a very clear description of the processes that generate
chemical gradients in biofilms, the genetic and physiological responses of
the bacteria and the techniques that can be used to measure the
microscale physiological heterogeneities of bacteria in biofilms.
8.

Hoiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O: Antibiotic

resistance of bacterial biofilms. Int J Antimicrob Agents 2010,
35:322-332.

9. Levin BR, Rozen DE: Non-inherited antibiotic resistance. Nat

 Rev Microbiol 2006, 4:556-562.
This review presents in vitro and in vivo evidence for the different forms of
non-inherited resistance to antibiotics in bacteria and the mechanisms
responsible. It is shown how non-inherited resistance could extend the
duration of antibiotic treatment, cause treatment failure and promote the
generation and ascent of inherited resistance in treated patients.

adherence and biofilm formation using analogues of the SspB

peptide. Arch Oral Biol 2010, 55:754-762.
16. Sharon N, Ofek I: Safe as mothers milk: carbohydrates as
future anti-adhesion drugs for bacterial diseases. Glycoconj J
2000, 17:659-664.
17. Lane JA, Mehra RK, Carrington SD, Hickey RM: The food
glycome: a source of protection against pathogen
colonization in the gastrointestinal tract. Int J Food Microbiol
2010, 142:1-13.
18. Moon HW, Bunn TO: Vaccines for preventing enterotoxigenic
Escherichia coli infections in farm animals. Vaccine 1993,
11:200-213.
19. Yang L, Liu Y, Wu H, Hoiby N, Molin S, Song Z-j: Current
understanding of multi-species biofilms. Int J Oral Sci 2011,
3:74-81.
20. Bowen WH, Koo H: Biology of Streptococcus mutans-derived
 glucosyltransferases: role in extracellular matrix formation of
carogenic biofilms. Caries Res 2011, 45:69-86.
This is the most updated review describing at the molecular level the
activity of S. mutans glucosyltransferases, the enzymes involved in the
matrix formation of the cariogenic biofilm.
21. Palombo EA: Traditional medical plant extracts and natural
products with activity against oral bacteria: potential

application in the prevention and treatment of oral disease.
Evid Based Complement Alternat Med 2009, 2011: (Article ID
680354).
In this very recent article, the author reviews plant extracts or phytochemicals that inhibits the growth of oral pathogens, influence bacterial
adhesion, reduce the development of biofilms and reduce the symptoms
of oral diseases.
22. Signoretto C, Bianchi F, Burlacchini G, Sivieri F, Spratt D,
Canepari P: Drinking habits are associated with changes in the

dental plaque microbial community. J Clin Microbiol 2010,
48:347-356.
This article gives the first description, by applying updated molecular
methods, that habits of drinking beverages known to be rich in polyphenols may affect the oral microbiota towards less pathogenic bacteria,
thus supporting the potential basis of phytochemical therapy.
23. Signoretto C, Canepari P, Pruzzo C, Gazzani G: Anticaries and
antiadhesive properties of food constituents and plant
extracts and implications for oral health. In Food Constituents
and Oral Health: Current Status and Future Prospects. Edited by
Wilson M. Woodhead Publishing Limited; 2009:240-262.
24. Otake S, Makimura M, Kuroki T, Nishihara Y, Hirasawa M:
Anticaries effects of polyphenolic compounds from Japanese
green tea. Caries Res 1991, 25:438-443.
25. Joiner A, Muller D, Elofsson UM, Arnebrant T: Elipsometry
analysis of the in vitro adsorption of tea polyphenols onto
salivary pellicles. Eur J Oral Sci 2004, 112:510-515.
26. Nakahara K, Kawabata S, Ono H, Ogura K, Tanaka T, Ooshima T,
Hamada S: Inhibitory effect of oolong tea on
glucosyltransferases of mutans streptococci. Appl Environ
Microbiol 1993, 59:968-973.

10. Bernbom N, Jorgensen RL, Ng YY, Meyer RL, Kingshott P,

Vejborg RM, Klemm P, Besenbacher F, Gram L: Bacterial
adhesion to stainless steel is reduced by aqueous fish extract
coatings. Biofilms 2006, 3:25-36.

27. Sakanaka S, Aizawa M, Kim M, Yamamoto T: Inhibitory effects of

green tea polyphenols on growth and cellular adherence of an
oral bacterium, Porphyromonas gingivalis. Biosci Biotechnol
Biochem 1996, 60:745-749.

11. Zhao L, Chu PK, Zhang Y, Wu Z: Antibacterial coatings on

titanium implants. J Biomed Mater Res B Appl Biomater 2009,
91:470-480.

28. Okamoto M, Sugimoto A, Leung KP, Nakayama K, Kamaguki A,

Maeda N: Inhibitory effect of green tea catechins on cysteine
proteinases in Porphyromonas gingivalis. Oral Microbiol
Immunol 2004, 19:118-120.

12. Maresso AW, Schneewind O: Sortase as a target of antiinfective therapy. Pharmacol Rev 2008, 60:128-141.
13. Chen L, Wen YM: The role of bacterial biofilm in persistent
infections and control strategies. Int J Oral Sci 2011, 3:66-73.

29. Okamoto M, Leung KP, Ansai T, Sugimoto A, Maeda N: Inhibitory

effect of green tea catechins on protein tyrosine phosphatase
in Prevotella intermedia. Oral Microbiol Immunol 2003,
18:192-195.

14. Svensson M, Platt FM, Svanborg C: Glycolipid receptor

depletion as an approach to specific antimicrobial therapy.
FEMS Microbiol Lett 2006, 258:1-8.

30. Shmuely H, Ofek I, Weiss EI, Rones Z, Houri-Haddad Y: Cranberry

components for the therapy of infectious disease. Curr Opin
Biotechnol 2011, this issue

15. Okuda K, Hanada N, Usui Y, Takeuchi H, Koba H, Nakao R,

Watanabe H, Senpuku H: Inhibition of Streptococcus mutans

31. Daglia M, Tarsi R, Papetti A, Grisoli P, Dacarro C, Pruzzo C,

Gazzani G: Antiadhesive effect of green and roasted coffee on

www.sciencedirect.com

Current Opinion in Biotechnology 2011, 23:18

Please cite this article in press as: Signoretto C, et al. Functional foods and strategies contrasting bacterial adhesion, Curr Opin Biotechnol (2011), doi:10.1016/j.copbio.2011.08.006

COBIOT-939; NO. OF PAGES 8

8 Food biotechnology

Streptococcus mutans adhesive properties on saliva-coated

hydroxyapatite beads. J Agric Food Chem 2002,
50:1225-1229.
32. Stauder M, Papetti A, Mascherpa D, Schito M, Gazzani G,
Pruzzo C, Daglia M: Antiadhesion antibiofilm activities of high
molecular weight coffee components against Streptococcus
mutans. J Agric Food Chem 2010, 58:11662-11666.
33. Papetti A, Pruzzo C, Daglia M, Grisoli P, Bacciaglia A, Repetto B,
Dacarro C, Gazzani G: Effect of barley coffee on the adhesive
properties of oral streptococci. J Agric Food Chem 2007,
55:278-284.
34. Stauder M, Papetti A, Daglia M, Vezzulli L, Gazzani G, Varaldo PE,
Pruzzo C: Inhibitory activity by barley coffee components
towards Streptococcus mutans biofilm. Curr Microbiol 2010,
61:417-421.
35. Daglia M, Stauder M, Papetti A, Signoretto C, Giusto G,
Canepari P, Pruzzo C, Gazzani G: Isolation of red wine
components with anti-adhesion and anti-biofilm activity
against Streptococcus mutans. Food Chem 2010,
119:1182-1188.
36. Timothe J, Bonsi IA, Padilla-Zakour IP, Koo H: Chemical
characterization of red wine grape (Vitis vinifera and Vitis
interspecific hybrids) and pomace phenolic extracts and their
biological activity against Streptococcus mutans. J Agric Food
Chem 2007, 55:10200-10207.
37. Shouji N, Takada K, Fukushima K, Hirasawa M: Anticaries effect
of a component from shiitake (an edible mushroom). Caries
Res 2000, 34:94-98.
38. Signoretto C, Marchi A, Bertoncelli A, Burlacchini G, Tessarolo F,
Caola I, Pezzati Q3 E, Zaura E, Papetti A, Lingstrom P et al.:
Effects of mushroom and chicory extracts on the physiology
and shape of Prevotella intermedia, a periodontopathogenic
bacterium. J Biomed Biotechnol, doi:10.1155/2011/635348, in
press.
39. Aimutis WR: Bioactive properties of milk proteins with
particular focus on anticariogenesis. J Nutr 2004,
134:989S-995S.
40. Johansson I, Lif Holgerson P: Milk and oral health. Nestle Nutr
Workshop Ser Pediatr Program 2011, 67:55-66.

Current Opinion in Biotechnology 2011, 23:18

41. Schupbach P, Neeser JR, Golliard M, Rouvet M, Guggenheim B:

Incorporation of caseinoglycomacropeptide and
caseinophosphopeptide into the salivary pellicle inhibits
adherence of mutans streptococci. J Dent Res 1996,
75:1779-1788.
42. Danielsson Niemi L, Hernell O, Johansson I: Human milk
compounds inhibiting adhesion of mutans streptococci to
host ligand-coated hydroxyapatite in vitro. Caries Res 2009,
43:171-178.
43. English HK, Pack AR, Molan PC: The effects of manukahoney on
plaque and gingivitis: a pilot study. J Int Acad Periodontol 2004,
6:63-67.
44. Badet C, Quero F: The in vitro effect of manuka honeys on growth
and adherence of oral bacteria. Anaerobe 2011, 17:19-22.
45. ooshima T, Minami T, Matsumoto M, Fujiwara T, Sobue S,
Hamada S: Comparison of cariostatic effects between regimes
to administer oolong tea polyphenols in SPF rats. Caries Res
1998, 32:75-80.
46. Ooshima T, Minami T, Aono W, Tamura J, Hamada S: Reduction
of dental plaque deposition in human by oolong tea extract.
Caries Res 1994, 28:146-149.
47. Signoretto C, Burlacchini G, Marchi A, Grillenzoni M, Cavalleri C,
Ciric L, Lingstrom P, Pezzati E, Daglia M, Zaura E, et al.: Testing a
low molecular mass fraction of a mushroom (Lentinus edodes)
extract formulated as an oral rinse in a cohort of volunteers.
J Biomed Biotechnol, doi:10.1155/2010/857987, in press.
48. Labrecque J, Bodet C, Chandad F, Grenier D: Effects of a
high-molecular-weight cranberry fraction on growth, biofilm
formation and adherence of Porphyromonas gingivalis.
J Antimicrob Chemother 2006, 58:439-443.
49. Yamanaka A, Kouchi T, Kasai K, Kato T, Ishihara K, Okuda K:
Inhibitory effect of cranberry polyphenol on biofilm formation
and cysteine proteases of Porphyromonas gingivalis.
J Periodontol Res 2007, 42:589-592.
50. Hirasawa M, Shouji N, Neta T, Fukushima K, Takada K: Three
kinds of antibacterial substances from Lentinus edodes
(Berk.) Sing. (Shiitake, an edible mushroom). Int J Antimicrob
Agents 1999, 11:151-157.

www.sciencedirect.com

Please cite this article in press as: Signoretto C, et al. Functional foods and strategies contrasting bacterial adhesion, Curr Opin Biotechnol (2011), doi:10.1016/j.copbio.2011.08.006