Biomedical Engineering Reference
In-Depth Information
S. epidermidis has been demonstrated in two animal models, a rat central
venous catheter-associated infection model and a mouse foreign-body in-
fection model.
61,62
Homologues of PIA are also found and identified in
many other staphylococcal species including S. aureus suggesting that it
might represent a more general pathogenicity principle in biofilm-related
infections.
63
PIA is a homoglycan composed of b-1,6-linked N-acetylglucosamine resi-
dues, synthesized by enzymes encoded in the icaADBC operon,
59
and confers
hydrophobic character to the Staphylococcus bacterial capsule.
64
Secretion of
PIA mediates initial adherence to material surfaces, interbacterial adhesion,
and facilitates biofilm formation.
65
Furthermore, PIA also mediates the
biocide resistance and protects against major components of human innate
host defense.
66
Therefore, the synthesis of PIA has been a general mech-
anism employed in biofilm formation by a diverse group of Gram-positive
and Gram-negative eubacteria. Its structure, function, and contribution to
S. epidermidis biofilm formation and pathogenesis of biomaterial-associated
infections have been reviewed.
67
Although PIA is a highly important factor in staphylococcal biofilm for-
mation, the biofilm-positive S. epidermidis strains have been isolated from
clinical relevant infections that produced PIA-independent biofilms, in
part mediated by the accumulation associated protein (Aap).
68
Such bio-
film accumulation proteins include Embp, Aap and BhP in S. epidermidis
and Bap in S. aureus.
69
Aap,a140kDaantigen,was shown to be a factor
essential in S. epidermidis accumulation on polymer surfaces. An antiserum
specific for Aap inhibited accumulation by up to 98% of the strains,
suggesting the novel immunotherapeutic strategies for prevention of
foreign body infection.
70
In fact, an immunotherapeutic approach is
becoming the new tool to combat staphylococcal infection, although no
anti-staphylococcal vaccines have yet successfully passed clinical trials.
71
So far, a limited number of targets have been examined for their immu-
notherapeutic potentials. One group of targeted compounds is MSCRAMM
that play an important role in bacterial adhesion to the biomaterial surface.
Other potential targets include factors that influence cell-cell interactions,
such as polysaccharide intercellular adhesin and proteinaceous inter-
cellular adhesin. The development and challenges of these vaccine targets
for
d
n
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4
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.
immunotherapeutic approaches have been excellently
reviewed
recently.
72,73
13.2.3 Maturation and Dispersal of Biofilm
After attachment to a surface, bacteria undergo further adaptation and
form a mature biofilm. The synthesis of EPS and antibiotic resistance are
further developed in this process. Biofilm maturation comprises adhesive
processes that link bacteria together during proliferation and disruptive
processes that form channels in the biofilm structure.
74
The latter is ne-
cessary for nutrients to reach cells in deeper biofilm layer, and also causes
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