Biofilms are microbial communities that are characterized by the presence of a viscoelastic extracellular polymeric substance (EPS). Studies have shown that polysaccharides, along with proteins and DNA, are a major constituent of the EPS, and play a dominant role in mediating its microstructure and rheological properties. Here, we investigate the possibility of entanglements and associative complexes in solutions of extracellular polysaccharide intercellular adhesin (PIA) extracted from Staphylococcus epidermidis biofilms. We report that the weight average molar mass and radius of gyration of PIA isolates are 2.01 × 105 ± 1200 g/mol and 29.2 ± 1.2 nm respectively. The coil overlap concentration, c*, was thus determined to be (32 ± 4) × 10−4 g/mL. Measurements of the in situ concentration of PIA (cPIA,Biofilm) was found to be (10 ± 2) × 10−4 g/mL. Thus, cPIA,Biofilm < c* and the amount of PIA in the biofilm is too low to cause polymer chain entanglements. In the pH range 3.0 to 5.5, PIA was found to both self-associate and to form complexes with bovine serum albumin (BSA). By static light scattering, both self-association and complex formation with 0.5 %(w/v) BSA were found to occur at PIA concentrations of 0.30 × 10−4 g/mL and greater, which is about 30 times lower than the measured cPIA,Biofilm. These results suggest that the microscopic origin of EPS viscoelasticity is unlikely to be due to polysaccharide entanglements. Furthermore, the onset of self-association and protein complexation of PIA occurs at concentrations far lower than the native PIA concentration in biofilms. This finding therefore suggests a critical role for those two association mechanisms in mediating biofilm viscoelasticity.

Biofilms production is a central feature of nosocomial infection of catheters and other medical devices used in resuscitation and critical care. However, the very effective biofilm forming pathogen Staphylococcus epidermidis often produces a modest host inflammatory response and few of the signs and symptoms associated with more virulent pathogens. To examine the impact of bacterial biofilm formation on provocation of an innate immune response, we studied the elaboration of the major complement anaphylatoxin C5a by human serum upon contact with S. epidermidis biofilms. Wildtype S. epidermidis and mutants of sarA (a regulatory protein that promotes synthesis of the biofilm-forming polysaccharide intercellular adhesin, PIA) and icaB (responsible for post-export processing of PIA) were studied. C5a release, as a function of exposed biofilm surface area, was on the order of 1 fmol cm−2 sec−1 and was dependent on the presence of PIA. Experimental results were used to inform a physiologically-based pharmacokinetic model of C5a release by an infected central venous catheter, one of S. epidermidis' primary means of causing human disease. These simulations revealed that the magnitude of C5a release on a superior vena cava catheter completely covered with S. epidermidis would be lower than necessary to alert circulating leukocytes. Combined, the experimental and computational results are highly consistent with clinical observations in which the clinical signs of central line associated bloodstream infection are often muted in association with this important pathogen.

Szafranski J. Combination octreotide, midodrine, and albumin may improve survival in patients with hepatorenal syndrome, but the evidence is weak. Clin. Res.