, 2007). The biofilm serves as a skeleton for large numbers of bacteria within a single structure and confers the population of interacting organisms with protection, one of the hallmarks of multicellular organisms. Extending the skeletal

metaphor, the biofilm matrix also plays important roles in signaling control and nutrient availability. Rheological studies by Stoodley and colleagues have demonstrated that the hydrated EPS matrix is highly viscoelastic and can be rapidly remodeled Pifithrin�� in response to changes in shear and other environmental stressors (Dunsmore et al., 2002; Klapper et al., 2002; Stoodley et al., 2002; Towler et al., 2003; Shaw et al., 2004). Thus, in this regard, it displays qualities similar to endochondral bone in that the strength of the extracellular matrix is modifiable by the cellular component in accordance with the external load. Detailed imaging and metabolic studies spurred by the development of the confocal microscope and PCR-based diagnostics have revealed that many disease conditions that were previously thought of as being chronic inflammatory in nature are actually indolent bacterial biofilm infections. These include osteomyelitis associated with S. aureus and Staphylococcus

epidermidis (Marrie & Costerton 1985; Costerton, 2005); gall bladder disease (Sung et al., 1991; Stewart et al., 2007); various chronic middle-ear disease processes associated with H. influenzae, S. pneumoniae, TSA HDAC in vivo Moraxella catarrhalis, and Pseudomonas aeruginosa including otitis media with effusion, recurrent otitis media, and otorrhea (Rayner et al., 1998; Ehrlich et al., 2002; Post et al., 2004; Dohar et al., 2005; Hall-Stoodley et al., 2006; Bakaletz, 2007; Kerschner et al., 2007; Post & Ehrlich, 2007, 2009; Apicella, 2009); chronic rhinosinusitis associated with H. influenzae, S. aureus, and other bacteria (Palmer, 2006; Sanderson Sirolimus clinical trial et al., 2006; Psaltis et al., 2007; Prince et al.,

2008); cholesteatoma associated with P. aeruginosa (Chole & Faddis, 2002); tonsillitis (Chole & Faddis, 2003); and adenoiditis associated with H. influenzae, S. pneumoniae, and M. catarrhalis (Zuliani et al., 2006; Nistico et al., 2009). In addition, there is substantial evidence to support a bacterial biofilm etiology for many chronic infections of the urogenital systems of both men and women including cystitis, prostatitis, vaginitis, and endometritis (Nickel et al., 1994; Hua et al., 2005; Swidsinski et al., 2008), and recently, both S. aureus and S. epidermidis have been demonstrated to form biofilms at surgical site infections (Kathju et al., 2009). Biofilms are also associated with dental infections including plaque, endodontitis (Carr et al.