(584aq) Multifunctional Bacterial Lyases: Roles in Disease and Therapeutic Applications

Stenotrophomonas maltophilia is a gram-negative, obligate aerobic bacteria widely distributed throughout the environment, particularly in water sources or damp environments. S. maltophilia is among the most common, emerging multi-drug resistant (MDR) organisms found in the lungs of people with chronic infections as well as with cystic fibrosis (CF). The prevalence of S. maltophilia in lung infections is increasing, with multiple studies pointing to S. maltophilia as an independent predictor of pulmonary exacerbation requiring hospitalization. A common mechanism of persistence during chronic infection is through biofilm formation, in which exopolysaccharide (EPS), DNA and other components are secreted into the extracellular space to form a barrier preventing access for antimicrobials and other therapeutics. We recently identified a family of unique polysaccharide lyases that exhibit broad substrate specificity against a range of EPS components. Strikingly, in contrast to other lyases, we find substrate specificity is highly dependent on pH, with activity against both mammalian polysaccharides as well as bacterial substrates. The possible role of dual substrate specificity in virluence and approaches for therapeutic intervention will be discussed.