“In my role as a Ph.D. mentor, I seek to provide students with the best possible environment to conduct research. This involves fostering an atmosphere conducive to learning and the free exchange of ideas. I strive to maintain and promote such an environment.”

Molecular Analysis of Pseudomonas aeruginosa Pathogenesis

The major goal of our laboratory is to understand the molecular etiology and pathogenesis of the bacterium Pseudomonas aeruginosa. This soil and water organism is particularly interesting since it is a common, yet serious opportunistic pathogen. Additionally, P. aeruginosa causes severe pulmonary infections in patients with the genetic disease cystic fibrosis (CF). Failure to control colonization with P. aeruginosa in CF patients is now the major cause of pulmonary debilitation in this group. Our research has centered on identifying and characterizing the genes involved in the regulation of several P. aeruginosa virulence factors. Molecular, biochemical and genetic techniques are used address these issues.

We are currently investigating the biosynthesis and genetic regulation of several polysaccharides (alginate, psl, pel), which play a role in the pathogenesis of P. aeruginosa. These polysaccharides contribute to the formation of biofilms in the CF lung and this plays a crucial role in the unusually high resistance of P. aeruginosa to natural defenses, clearance mechanisms and therapeutic control in CF.

We are also investigating other properties of P. aeruginosa which are coordinately expressed with alginate genes. For example, many mucoid P. aeruginosa isolates obtained from chronic lung infections are nonmotile and fail to synthesize flagella. This state may represent an adaptive response of the organism for growth in a protective biofilm within the CF lung environment. Chronic lung infections caused by P. aeruginosa in CF patients are extremely difficult to control since the bacteria exhibit a biofilm-mode of growth rendering P. aeruginosa resistant to antimicrobials and phagocytic cells.

Our hypothesis is that motility is required in the initial stages of the developing biofilm and that alginate polysaccharide is essential at a later stage. Since the ability of P. aeruginosa to grow as a biofilm in the lungs of CF patients is a critical feature of the pathogenesis of this chronic infection, an understanding of developmental events which occur during the process of biofilm formation is essential.

Publications

Robert W. Huigens, L. Ma, C. Gambino, P.D.R. Moeller, A. Basso, J. Cavanagh, D.J. Wozniak, and C. Melander.  2008.  Control of bacterial biofilms with marine alkaloid derivatives.  Mol. BioSyst. In press.

Belete, B., H. Lu, and D.J. Wozniak.  2008. Pseudomonas aeruginosa AlgR regulates type IV pilus biosynthesis by activating expression of the fimU-pilVWXY1Y2E operon. J. Bacteriol. 190:2023-2030.

Andrew J. Leech, A. Sprinkle, L. Wood, D.J. Wozniak, and D.E. Ohman.  2008.  The NtrC-family regulator AlgB, which controls alginate biosynthesis in mucoid Pseudomonas aeruginosa, binds directly to the algD promoter.  J. Bacteriol. 190:581-589.

Hans-Curt Flemming, T, R. Neu, and D.J. Wozniak.  2007. The EPS matrix: The “house of biofilm cells.”  J. Bacteriol. 189:7945-7947.

Luyan Ma, H. Lu, A. Sprinkle, M. R. Parsek, and D.J. Wozniak.  2007. Pseudomonas aeruginosa Psl is a galactose- and mannose-rich exopolysaccharide.  J. Bacteriol. 189:8353-8356.

Ryder, C., M. Byrd, and D.J. Wozniak.  2007. Role of polysaccharides in Pseudomonas aeruginosa biofilm development.  Current Opinion in Microbiology.  10:1-5.

Sanders, L.H., A. Rockel, H. Lu, D. J. Wozniak, and M.D. Sutton.  2006 Role of Pseudomonas aeruginosa dinB-encoded DNA polymerase IV in mutagenesis. J. Bacteriol. 188: 8573-8585.

Ma, L., K.D. Jackson, R.M. Landry, M.R. Parsek, and D.J. Wozniak. Analysis of Pseudomonas aeruginosa conditional Psl variants reveals roles for the Psl polysaccharide in adhesion and maintaining biofilm structure post-attachment.  J. Bacteriol. 188: 8213-8221.

Tart, A.H., M.J. Blanks, and D. J. Wozniak.  2006.  The AlgT-dependent transcriptional regulator AmrZ (AlgZ) inhibits flagellum biosynthesis in mucoid, non-motile Pseudomonas aeruginosa cystic fibrosis isolates.  J. Bacteriol. 188. 6843-6849.

PubMed link to Wozniak DJ