Novel Targets for Treatment of Pseudomonas aeruginosa Biofilms - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 258

reactions because they do not bind to human Fc receptors or complement system
(Larsson et al. 1993 ), and should thus be safe. The IgY egg yolk antibodies were
found by Nilsson et al. to bind flagellin as the major antigen (Nilsson et al. 2007 ).
Flagellin is the main protein of the flagella and is crucial for establishing infections
in hosts as well as being involved in chemotaxis, motility, and adhesion. As a
consequence, anti-Pseudomonas IgY has been shown to prevent adhesion of
Pseudomonas to dermal epithelial cells in vitro. A secondary positive effect of
binding flagellin is the potential to dampen local inflammation since the accessi-
bility of the bacteria to TLR5 is attenuated (Smith et al. 2003 ; Shanks et al. 2010 ).
Flagella are very abundant in bacteria and hence egg yolk antibodies have been
shown to be immunoreactive against several strains of P. aeruginosa (Nilsson
et al. 2007 ).
In a long-term study (12 years) of oral treatment with anti-pseudomonas egg
yolk antibodies, a significantly lower number of positive P. aeruginosa cultures
were found in the treated group compared to the control group (2.3 vs. 7 per
100 treatment months). In addition, a lower incidence of chronic P. aeruginosa
infection was found in the treatment group. Although the data were collected from a
small number of patients (17 vs. 23), the data strongly suggest that prophylaxis with
a combination of anti-pseudomonas antibodies and antibiotics has great potential
(Nilsson et al. 2007 , 2008 ).
Fully human IgG1 monoclonal antibodies, targeting flagellin type b, have
recently been found to markedly decrease P. aeruginosa motility and to improve
survival of mice in a lethal pulmonary mouse model using a multidrug-resistant
P. aeruginosa strain (Adawi et al. 2012 ). The authors found that a double dose
paradigm administered postinfection, kept 75 % of the mice alive until day 7 com-
pared to 20 % in the formulation- and isotype control (Adawi et al. 2012 ). Several
similar studies have found that anti-flagellin antibodies can reduce mortality and
morbidity in murine P. aeruginosa -infected burn models (Pollack et al. 1984 ;
Barnea et al. 2006 , 2009 ).
From the information above, it is clear that prophylactic treatment with anti-
bodies has overcome initial disappointing clinical studies and now seems to be a
persuasive and promising treatment regime (Bone 1991 , 1996 ).
8 Perspectives for Future Treatment
Infections with aggregating bacteria have proven to be hard to prevent and treat.
Recent findings of biofilm and aggregate heterogeneity have opened a window of
novel treatment strategies. Research has shown that distinct subpopulations have
different susceptibility to antimicrobials and therefore the biofilm should preferably
be eradicated with more than one regimen. Combinations of already approved
antimicrobials have shown good results in vivo, but new combinations including
novel compounds such as QSIs, DNase, silver, or antibodies could ultimately be the
end of chronic infections. The synergistic use of these novel drugs in combination