Scott J. Hultgren
Election Year: 2011
Primary Section: 44, Microbial Biology
Membership Type: Member
Our studies blend multiple scientific disciplines elucidating bacterial and host mechanisms that determine the onset, course and outcome of interactions between a host mucosal surface and bacterial pathogens. Using genetics, genomics, biochemistry, structural biology, high-resolution imaging, animal models, clinical studies and combinatorial chemistry, we have illuminated how bacterial intracellular lifestyles and community behaviors play critical roles in urinary tract infection (UTI). We uncovered principles of adhesive pili biogenesis in Gram-negative bacteria of the chaperone/usher pathway; delineating molecular details of donor strand complementation and exchange mechanisms by which subunit folding is coupled with translocation and assembly of pili across the outer membrane. We delineated how uropathogenic E. coli use type 1 pili to invade and establish biofilm-like intracellular bacterial communities within bladder cells subverting extracellular host defenses and how quiescent intracellular reservoirs can seed recurrent infection. We identified complex networks governing mucosal epithelial responses that determine disease outcome. Further, we elucidated a mechanism by which bacteria form a directed biofilm-associated amyloid fiber called curli. Together, our work is changing the way UTIs are evaluated, re-shaping models of bacterial infections in general and spawning new technologies to design novel vaccines and anti-microbial therapeutics to diagnose, treat and/or prevent UTIs and their sequelae.