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Alan R. Hauser, MD, PhDAssistant Professor
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To visit the Hauser Lab website click here.
Pseudomonas aeruginosa is a gram-negative opportunistic bacterium and a major cause of hospital-acquired pneumonia, bloodstream infections, and urinary tract infections in humans. Although many putative P. aeruginosa virulence factors have been identified, much remains unclear regarding the mechanisms by which this bacterium colonizes, invades, and disseminates within its host.
We investigate the mechanisms by which P. aeruginosa interacts with host cells to cause disease. A particular interest of the lab is the role of the type III secretion system in pathogenesis. Type III secretion pathways form needle-like apparatuses that actually inject toxins directly into the cytoplasm of host cells. They are used by many gram-negative bacteria to injure or kill human cells and thus cause disease. We focus on the interaction of the secreted toxins with the host. Type-III-secreted toxins are characterized using molecular techniques, while tissue culture and mouse models of pneumonia are used to examine the effects these toxins have on the host and to characterize their roles in disease. Current projects involve the use of molecular techniques to study mechanisms of toxin-mediated host cell injury and investigation of the interaction between toxins and the host immune system.
In a second project, we are examining why some P. aeruginosa strains are much more virulent than others. These investigations have led to the identification of several novel virulence factors that are produced by some strains but not others. We plan to expand these studies to identify additional novel virulence factors and to explore the mechanism by which these factors enhance disease severity.
The common theme of these projects is to better understand the mechanisms by which P. aeruginosa causes disease. Such knowledge will lead to novel therapeutic approaches to P. aeruginosa infections. In addition, these bacterial factors may prove to be powerful tools useful in the dissection of eukaryotic cell signaling pathways.
Ottman, C., L. Yasmin, M. Weyand, J. L. Veesenmeyer, M. H. Diaz, R. H. Palmer, M. S. Francis, A. R. Hauser, A. Wittinghofer, and B. Hallberg. 2007. Phosphorylation-independent interaction between 14-3-3 and Exoenzyme S: from structure to pathogenesis. EMBO J. 26:902-913.
Matz, C., A. M. Moreno, M. Alhede, M. Manefield, A. R. Hauser, M. Givskov, S. Kjelleberg. 2008. Pseudomonas aeruginosa uses type III secretion system to kill biofilm-associated amoebae. ISME J. 2:843-852.
Diaz, M. H., C. M. Shaver, J. D. King, S. Musunuri, J. A. Kazzaz, A. R. Hauser. 2008. Pseudomonas aeruginosa induces localized immunosuppression during pneumonia in mammals. Infect. Immun. 76:4414-4421.
Battle, S. E., F. Meyer, J. Rello, V. L. Kung, A. R. Hauser. 2008. The hybrid pathogenicity island PAGI-5 contributes to the highly virulent phenotype of a Pseudomonas aeruginosa isolate in mammals. J. Bacteriol. 190:7130-7140.
Jain, M., M. Bar-Meir, S. McColley, J. Cullina, E. Potter, C. Powers, M. Prickett, R. Seshadri, B. Jovanovic, A. Petrocheilou, J. D. King, A. R. Hauser. 2008. Evolution of Pseudomonas aeruginosa type III secretion in cystic fibrosis: a paradigm of chronic infection. Translat. Res. 152:257-264.
Battle, S. E., J. Rello, A. R. Hauser. 2009. Genomic islands of Pseudomonas aeruginosa. FEMS Microbiol. Lett. 290:70-78.
Rice, S. A., C. H. Tan, P. J. Mikkelsen, V. Kung, J. Woo, M. Tay, A. Hauser, D. McDougald, J. S. Webb, S. Kjelleberg. 2009. The biofilm life-cycle and virulence of Pseudomonas aeruginosa are dependent on a filamentous prophage. ISME J. 3:271-282.
Veesenmeyer, J. L., A. R. Hauser, T. Lisboa, J. Rello. 2009. Pseudomonas aeruginosa virulence and therapy: What’s new and why it matters. Crit. Care Med. 37:1777-1786.
Scheetz, M. H., M. Hoffman, M. K. Bolon, G. Schulert, W. Estrellado, I. G. Baraboutis, P. Sriram, M. Dinh, L. K. Owens, A. R. Hauser. 2009. Morbidity associated with Pseudomonas aeruginosa bloodstream infections. Diag. Microbiol. Infect. Dis. 64:311-319.
Hauser, A. R. The Type III secretion system of Pseudomonas aeruginosa: Infection by injection. Nat. Rev. Microbiol. In press.
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View Publications by Alan Hauser listed in the National Library of Medicine (PubMed). |
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