Biomedical Engineering Reference
In-Depth Information
4.2 New strategies based on research in
Candida
-biofilm biology
The decreased susceptibility of yeast biofilms to classical antifungal drugs encouraged
scientists to explore other means to inhibit
Candida
and to limit the deleterious effects of its
biofilm. Knowledge of interactions between
Candida
and oral tissues and between
Candida
and oral bacteria should present new perspectives for therapy. Microorganisms in biofilms
(yeast included) are less sensitive to antimicrobial agents than free microorganisms in
suspension. Authors (Thurnheer et al., 2003) have shown a decreased drug diffusion rate
through polyspecies biofilms, containing
Candida
among others, proportional to the cubic
root of the drug's marker molecular weight, suggesting the deviousness of the diffusion
route through biofilm depth as the cause of delay in molecule penetration. Nevertheless,
drug resistance could also be attributed to metabolic properties and gene expression
induced by microorganisms living in the community and to the production of an
extracellular matrix.
Other
in vitro
studies (reviewed by Nobile et al., 2006) suggest several molecular factors that
explain biofilm development and biofilm drug resistance, such as specific biofilm
phenotypes (Finkel & Mitchell, 2011), adhesins, cell to cell communication, and quorum
sensing (Deveau & Hogan, 2011). The link between hyphae production and
Candida
biofilm
development
in vitro
and between hyphae production and pathological conditions
in vivo
led to the investigation of the genetic regulation of hyphal morphogenesis. The rapid
initiation of biofilm in the presence of new surfaces available for anchoring oriented the
genetic analysis towards a gene expression distinct from that found in the planktonic state.
Quorum sensing pathways that allow microorganism colonies (including yeast) to sense
their cell density involve small molecules such as farnesol and tyrosol. The former is known
to promote resistance against oxidative stress and inhibit hyphal morphogenesis and biofilm
formation, whereas the latter is a putative biofilm facilitator. The (over)expression and
polysaccharidic matrix production of adhesins is also linked to biofilm formation. All of
these biological characteristics contribute to make
Candida
biofilms “a well-designed
protected environment” (Mukherjee P. et al., 2005). A better knowledge of molecular events
in
Candida
biofilm formation could present new strategies to prevent oral candidiasis
contracted from biomaterials inserted in the oral cavity.
4.3 New strategies based on research in exocrine biology
Antimicrobial molecules/systems derived from exocrine secretions are interesting topics of
research. Studies
in vitro
have already shown the benefits of lysozyme, lactoferrin, histatin
(Pusateri et al., 2009), and peroxidase systems with thiocyanate, chloride, and especially
iodide. However, transferring such data to
in vivo
studies hasn't yet provided the expected
results because of the immense complexity of the oral environment. Again, the publication
of large clinical studies is still being awaited.
Research in peroxidase biology is an illustrative example of the multiple facets of
knowledge transfer from fundamental sciences to clinical applications. In the presence of
hydrogen peroxide, for example, peroxidases in exocrine secretions are able to catalyze the
production of hypohalous compounds that carry an antimicrobial effect: hypoiodite
in vitro
and hypothiocyanite in saliva. Previous studies have shown that a 30-minute exposure to
hypoiodite was sufficient to inhibit planktonic growth
in vitro
(Majerus & Courtois, 1992).
Moreover, the development of
Candida
biofilm on material surfaces could be reduced or
even suppressed by lactoperoxidase-generated hypoiodite and hypothiocyanite. This was
