Scott J. Hultgren, Ph.D.

Helen L. Stoever Professor
Molecular Microbiology

Molecular Microbiology and Microbial Pathogenesis Program
Plant and Microbial Biosciences Program
Biochemistry, Biophysics, and Structural Biology Program
Molecular Cell Biology Program

  • 314-362-6772

  • 314-747-3627

  • 314-362-7042

  • 314-362-1998

  • 8230

  • 10260 McDonnell Pediatric Research Building

  • hultgren@wustl.edu

  • http://www.hultgrenlab.wustl.edu

  • bacterial pathogenesis, functional genomics, pilus biogenesis, host-pathogen interactions, structural biology

  • Pilus and amyloid fiber formation in bacteria: Structure, function and role in diseases of the urinary tract

Research Abstract:

My lab is using a blend of disciplines to understand the molecular details of host pathogen interactions in urinary tract infections (UTIs) caused by gram-negative Escherichia coli (UPEC) and gram-positive Enterococcus. Using genetics, biochemistry and x-ray crystallography, we have discovered a novel mechanism of donor-strand complementation and exchange by which the chaperone usher pathways of gram-negative bacteria assemble adhesive pili. We are investigating the role of pili at the host-pathogen interface and the function of the Cpx two-component signal transduction system that monitors pilus biogenesis. In addition, diverse technologies are being used to study the export and assembly of an extracellular bacterial amyloid fiber called curli. Using time lapse, confocal and electron microscopy, we have shown that piliated UPEC invade bladder epithelial cells. UPEC then activates a complex genetic program that leads to the development of intracellular bacterial communities (IBCs) that have biofilm-like characteristics. During IBC maturation, bacteria go through several developmental switches as evidenced by changes in growth rate, motility, adhesin expression and cellular morphology. Dispersal of the IBC leads to the coordinated burst of thousands of UPEC into the bladder lumen, impacting transmission. The IBC maturation program facilitates subversion of early innate defenses including TLR4-signaling. The genome sequence of our model UPEC has been determined and functional genomics, mutational and promoter fusion analyses are being used to probe the role of specific genetic cascades throughout the infection cycle. This work is spawning new insights into infectious diseases, their relationship to cancer and better strategies for treatment and prevention of UTIs.

Selected Publications:

Justice SS, Hung CS, Theriot JA, et al. Differentiation and developmental pathways of uropathogenic E. coli in urinary tract pathogenesis. Proc Natl Acad Sci USA 2004 101:1333-1338.

Anderson GG, Palermo JJ, Roth R, Heuser J, Hultgren SJ. Intracellular bacterial biofilm-like pods in urinary tract infections. Science 2003 301 105-107.

Schilling JD, Martin SM, Hung C, Lorenz RG, Hultgren SJ. TLR4 on stromal and hematopoietic cells mediates innate resistance to uropathogenic E. coli. Proc Natl Acad Sci USA 2003 100:4203-4208.

Chapman MR, Robinson LS, Pinkner JS, et al. Escherichia coli curli operons direct amyloid fiber formation. Science 2002 295:851-855.

Sauer FG, Pinkner JS, Waksman G, Hultgren SJ. Chaperone priming of pilus subunits facilitates a topological transition that drives fiber formation. Cell 2002 111:1-20.

Last Updated: 8/4/2011 10:04:37 AM

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