Northwestern University Feinberg School of Medicine

Alan Hauser Laboratory

Our Research

Pseudomonas aeruginosa

Pseudomonas aeruginosa is a gram-negative opportunistic bacterium and a major cause of healthcare-associated 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 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, the development of new therapies, and investigation of the interaction between toxins and the host immune system.

In a second project, we are using comparative genomic approaches to examine why some bacterial strains are more virulent than others.  These investigations have been applied to P. aeruginosa as well as other healthcare-associated bacteria such as Acinetobacter baumannii and carbapenem-resistant Klebsiella pneumoniae (CRE strains).  To date, studies have led to the identification of several genetic elements that encode novel virulence factors made by some strains but not others.  One such element, RhsT, over-activates the inflammasome to cause excessive inflammation. We plan to expand these studies to identify additional novel accessory genomic elements and virulence factors and to explore the mechanism by which these factors enhance disease severity.

New projects in the lab include translational approaches that utilize small-molecule inhibitors and nanoparticles as potential therapeutic strategies. The common theme of all the projects being explored by the lab is to better understand the mechanisms by which multidrug-resistant bacteria cause disease and to use this knowledge to block these mechanisms.  In addition, these bacterial factors may prove to be powerful tools for the dissection of eukaryotic cell signaling pathways.