|September 18, 2014
Bldg. 440, A105-106
"Stenotrophomonas maltophilia: From Nocosomal Pathogen to Nanoparticle," by Bryan W. Berger, Lehigh University, hosted by Gary Christopher
Abstract: Stenotrophomonas maltophilia is a ubiquitous, gram-negative bacteria that has become an increasing important, multidrug-resistant (MDR) nocosomial pathogen in immunocompromised patients. One unique mechanism that S. maltophilia has evolved to become MDR is its production of highly branched, anionic exopolysaccharides (EPS) to form biofilms. Recent studies indicate the additional negative charge of S. maltophilia EPS due to the branched HexA-Lac group enables biofilm binding to metallic or plastic surfaces, as well as creating a heat-, acid-, and detergent-resistant environment that allows S. maltophilia to colonize water purification systems, ventilators and stents. As a result, S. maltophilia is the second leading cause of ventilator-associated pneumonia, with over 70% of all S. maltophilia-specific, ventilator-associated MDR infections caused by biofilm formingstrains.
First, I will discuss our recent work identifying and characterizing a series of novel polysaccharide lyases (PLs) unique to clinical isolates of S. maltophilia. PLs are a broad class of enzymes that depolymerize polysaccharides via a b-elimination mechanism. We find that in contrast to pathogens such as P. aeruginosa that produce PLs specific to a particular EPS, S. maltophilia PL smlt1473 exhibits broad substrate specificity, but with strict pH regulation of activity against a given substrate. Furthermore, mutations to conserved regions flanking thepredicted active site provide further diversification of both enzymatic activity as well as possible substrates accepted by the PL. The basis for this versatility in both substrate specificity as well as pH-dependent suggests this class of enzymes has evolved considerably flexibility in order to process increasingly diverse biofilm EPS chemical structures as well as function as a possible virulence factor active against mammalian polysaccharide substrates such as hyaluronic acid.
Second, I will discuss mechanisms of heavy-metal resistance in S. maltophilia clinical isolates. We have identified a series of extracellular proteins that are responsible for conferring resistance to silver, lead, cadmium, and other toxic heavy metals at concentrations 10-100 fold greater than that of E. coli and other gram-negative bacterium. We have exploited these proteins to engineer strains with enhanced tolerance to a wide range of heavy metals that produce nanostructured metal sulfides with well-defined chemical and optical properties. Applications in scalable biosynthesis of nanostructured metal sulfides will be discussed.