Daniel Wozniak, PhD Daniel.wozniak@osumc.edu B.S., Biology, Aquinas College Ph.D., Microbiology, The Ohio State University Postdoc, Bacterial Pathogenesis, University of Tennessee Medical Center

Professor, Infectious Disease and Microbiology
Center for Microbial Interface Biology
Member, IBGP
Member, DHLRI
Adjunct Professor, Microbiology and Immunology, Wake Forest University Health Sciences.

Bacterial pathogenesis and gene regulation

The major goal of our laboratory is to understand the molecular biology and pathogenesis of the bacterium Pseudomonas aeruginosa. This soil and water organism 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 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 two polysaccharides called alginate and Psl, which are critical factors in biofilm formation and thus pathogenesis of P. aeruginosa.  Biofilms, which are defined as communities of microorganisms that are attached to a surface, play a critical role in infectious diseases.  Because of their innate resistance to antibiotics, phagocytic cells, and other biocides, biofilms are difficult, if not impossible, to eradicate. Since the matrix contributes considerably to the highly resistant nature of the biofilm, it is anticipated that this work will lead to agents that could disrupt the matrix and be of significant therapeutic value patients colonized with P. aeruginosa.  In this regard, we have ongoing collaborations with scientists to develop a conjugate vaccine for use in CF patients and to develop small molecule inhibitors of bacterial biofilms.

Among infectious diseases, respiratory infections are the leading cause of morbidity and a primary cause of death for children.  At OSU, I am part of a team of investigators that study the host-pathogen interface in persistent airway infections. The long-term goals of our laboratory are to deepen our understanding of the interplay between host immunity and bacterial biofilms and to develop therapies to prevent persistence of infectious childhood agents by eliminating initial infection or progression to the biofilm mode of growth.

E. T. Weimer, S. Ervin, D.J. Wozniak, and S.B. Mizel.  2009.  Immunization
of young African green monkeys with OprF epitope 8-OprI-type A- and
B-flagellin fusion proteins promotes the production of protective antibodies
against nonmucoid Pseudomonas aeruginosa.  Vaccine.  In press.
 
M. S. Byrd, I. Sadovskaya, E. Vinogradov, H. Lu, A. B. Sprinkle, S. H.
Richardson, L. Ma, B. Ralston, M. R. Parsek, E. M. Anderson, J. S. Lam, and
D. J. Wozniak. 2009.  Genetic and biochemical analyses of the Pseudomonas
aeruginosa Psl exopolysaccharide reveal overlapping roles for polysaccharide
synthesis enzymes in Psl and LPS production.  Mol. Microbiol. 73:622-638.
 
E. T. Weimer, H. Lu, D.J. Wozniak, and S.B. Mizel.  2009. A vaccine
containing OprF epitope 8, OprI, and type A and B flagellins provides
protection against Pseudomonas aeruginosa.  Infect. Immun.  77:2356-2366.
 
M. Starkey, J. H. Hickman, L. Ma, N. Zhang, S. De Long, A. Hinz, S.
Palacios, C. Manoil, M. J. Kirisits, T. Starner, D. J. Wozniak, C. S.
Harwood, M. R. Parsek.  2009. Pseudomonas aeruginosa rugose small colony
variants have adaptations that likely promote persistence in the cystic
fibrosis lung.  J. Bacteriol.  191:3942-3503.
 
L. Ma, M. Conover, H. Lu, M. R. Parsek, K. Bayles, and D.J. Wozniak. 2009.
Assembly and development of the Pseudomonas aeruginosa biofilm matrix.  PLoS
Pathogens.  5:e1000354.

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. 4(6):614-621.

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.

 P. J. Baynham, D. M. Ramsey, B. V. Gvozdyev, E. M. Cordonnier, and D. J. Wozniak.  2006. The Pseudomonas aeruginosa ribbon-helix-helix DNA-binding protein AlgZ (AmrZ) controls twitching motility and biogenesis of type IV pili. J. Bacteriol.  188:132-140.