Biofilms in Disease - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 7

density-dependent regulation (“quorum sensing,” QS) controls biofilm differentia-
tion in many microorganisms (Irie and Parsek 2008 ).
5 Biofilm Pathogens
While the general model of biofilm formation gives a good overall outline that is
applicable to many biofilm-forming bacteria, most biofilm microorganisms produce
highly specific biofilm factors. Some of those that were thoroughly investigated
shall briefly be introduced in the following.
Biofilm formation in P. aeruginosa is best understood, at least in vitro. This
species produces three main biofilm exopolysaccharides, the negatively charged
alginate, the mannose-rich neutral “Psl,” and the glucose-rich “Pel” exopolysac-
charides (Ryder et al. 2007 ). Production of alginate in particular is associated with
the “mucoid” phenotype of P. aeruginosa strains isolated from cystic fibrosis
infection (May et al. 1991 ). The impact of QS on biofilms was first described in
P. aeruginosa , where as in many other bacterial pathogens, it has a strong impact on
the production of biofilm factors and biofilm development in general (Davies
et al. 1998 ). QS regulation in P. aeruginosa involves at least three systems (Rhl,
Las, and Qsc) forming a QS network (Jimenez et al. 2012 ). Early experiments
performed in P. aeruginosa indicated that QS is a positive regulator of biofilm
expansion (Davies et al. 1998 ), but we know now that the impact of QS on biofilm
development is more complicated, affecting a series of factors involved in biofilm
growth and structuring (Joo and Otto 2012 ). Rhamnolipids, for example, are
QS-controlled surfactants that facilitate P. aeruginosa biofilm structuring (Boles
et al. 2005 ). Furthermore, pili (or fimbriae) in P. aeruginosa provide motility and
are not only important for reaching a surface, but also in QS-regulated detachment
processes (Gibiansky et al. 2010 ), where cells regain pili-mediated motility starting
in the center of biofilm “mushrooms” (Purevdorj-Gage et al. 2005 ).
S. aureus and coagulase-negative staphylococci contribute to a number of
biofilm infections and dominate among pathogens causing infections of indwelling
medical devices. Much of our knowledge on staphylococcal biofilm formation
stems from research on the human commensal S. epidermidis (Otto 2009 ).
S. epidermidis —as most other staphylococci—produces an exopolysacharide
termed polysaccharide intercellular adhesin (PIA) or poly- N -acetyl glucosamine
(PNAG). PIA/PNAG is a linear homopolymer of N -acetyl glucosamine with partial
de-acetylation that introduces positive changes in the otherwise neutral molecule
(Mack et al. 1996 ; Vuong et al. 2004b ). It has a demonstrated significant function in
in vitro and in vivo biofilm formation, although not all staphylococcal biofilm-
forming strains (especially S. aureus ) appear to rely on PIA/PNAG to form biofilms
(Rohde et al. 2007 ). A large number of proteins also contribute to the formation of
the staphylococcal biofilm matrix, such as the accumulation-associated protein Aap
(Conrady et al. 2008 ). The biofilm-structuring surfactant phenol-soluble modulin
(PSM) peptides of staphylococci are controlled by the accessory gene regulator