Thanks. Those are good and recent references.
Judy

Airway biofilms: implications for pathogenesis and therapy of
respiratory tract infections.
Kobayashi H.

First Department of Internal Medicine, Kyorin University School of
Medicine, Shinkawa, Mitaka, Tokyo, Japan. hkobaya@kyorin-u.ac.jp
[Treat Respir Med. 2005;4(4):241-53.]

The differentiation of bacterial biofilms in the airway environment,
the pathogenesis of airway biofilm, and possible therapeutic methods
are discussed. Biofilm diseases that characteristically involve the
respiratory system include cystic fibrosis (CF), diffuse
panbronchiolitis (DPB), and bronchiectasia with Pseudomonas aeruginosa
(P. aeruginosa) infection. There is evidence to suggest that almost
all strains of P. aeruginosa have the genetic capacity to synthesize
alginate, a main matrix of biofilms, when ecological conditions are
unfavorable for their survival. The bacteria inside the mature biofilm
show increased resistance to both antibacterials and phagocytic cells,
express fewer virulence factors because of their stationary state of
growth, and are less stimulatory to the mucosa because of the
'sandwich binding'. These factors facilitate both the colonization of
bacteria and their extended survival even under unfavorable
conditions. Since the biofilm limits colonization to a latent form,
the clinical symptoms in this situation are unremarkable. However, the
clinical progression of both CF and DPB proceeds in two characteristic
directions. The first is an acute exacerbation caused by planktonic
bacteria that have germinated from the biofilm. The second is a slow
progression of disease that is induced by harmful immune reactions.
The harmful reactions are mediated by alginate, which induces antigen
antibody reactions around the airways, as well as formation of
circulating immune complexes that are deposited on lung tissue.
Furthermore, the highest titer of bacterial permeability increasing
anti-neutrophil cytoplasmic autoantibodies (BPI-ANCA) is observed in
association with highly impaired pulmonary function in patients with
CF and DPB, as well as in patients with a lengthy period of
colonization with P. aeruginosa. BPI-ANCA subsequently makes chronic
airway infection even more intractable. The long-term use of 14- or 15-
ring membered macrolides results in a favorable clinical outcome for
patients with DPB and in some patients with CF. In the last 10 years,
an increasing number of studies have reported secondary actions of
macrolides that include effects on both airway and phagocytic cells,
as well as an anti-biofilm activity. The 14- or 15-ring membered
macrolides inhibit: (i) the alginate production from P. aeruginosa;
(ii) the antibody reaction to alginate, which leads to a decrease in
the immune complex formation; and (iii) the activation of the
autoinducer 3-O-C12-homoserine lactone and subsequent expression of
lasI and rhlI in quorum sensing systems in P. aeruginosa. These anti-
biofilm actions of macrolides may represent their basic mechanisms of
action on airway biofilm disease.

PMID: 16086598 [PubMed - indexed for MEDLINE]