David A. Hunstad, M.D.
Molecular Microbiology and Microbial Pathogenesis Program
6th Floor, McDonnell Pediatric Research Building
bacterial pathogenesis, Escherichia coli, host-pathogen interactions, innate immunity, novel therapeutics, urinary tract infection, kidney, pyelonephritis
Novel virulence mechanisms and therapeutics in E. coli urinary tract infection
Work in the Hunstad lab focuses on the interactions of pathogenic bacteria with their hosts. We aim to elucidate the modulation of host immune responses by pathogens and to determine the mechanisms by which these bacteria present specific virulence factors on their surfaces.
Currently, we use cultured bladder epithelial cell models and murine models of cystitis to investigate the ability of uropathogenic E. coli to modulate host innate and adaptive immune responses. In addition, we are studying the molecular mechanisms by which selected outer membrane proteins contribute to the virulence of uropathogenic Escherichia coli. Our primary goal is to discover novel targets for interventions that will prevent and treat bacterial infections of the urinary tract, gastrointestinal tract, and central nervous system. Along these lines, we are leveraging recent discoveries in UTI pathogenesis to design nanoparticle-based therapies for prevention of acute and recurrent UTI. We have also launched a translational study of immune responses to UTI in male and female infants, paired with a new model of male UTI in mice. Our new infection technique permits first-ever preclinical studies of sex differences in UTI pathogenesis, as well as robust modeling of ascending renal abscess formation, resolution, and fibrosis.
Olson PD, Hruska KA, Hunstad DA. Androgens enhance male UTI severity in a new murine model. J Am Soc Nephrol 2016; 27: 1625-1634. PMC4884108
Loughman JA, Yarbrough ML, Tiemann KM, Hunstad DA. Local generation of kynurenines mediates inhibition of neutrophil chemotaxis by uropathogenic Escherichia coli. Infect Immun 2016; 84: 1176-1183. PMC4807489
Danka ES, Hunstad DA. Cathelicidin augments epithelial receptivity and pathogenesis in experimental Escherichia coli cystitis. J Infect Dis 2015; 211: 1164-1173. PMC4366604
Wagers PO, Tiemann KM, Shelton KL, Kofron WG, Panzner MJ, Wooley KL, Youngs WJ, Hunstad DA. Imidazolium salts as small-molecule urinary bladder exfoliants in a murine model. Antimicrob Agents Chemother 2015; 59: 5494-5502. PMC4538537
Lim YH, Tiemann KM, Heo GS, Wagers PO, Rezenom YH, Zhang S, Zhang F, Youngs WJ, Hunstad DA,* Wooley KL.* Preparation and in vitro antimicrobial activity of silver-bearing degradable polymeric nanoparticles of polyphosphoester-block-poly(L-lactide). ACS Nano 2015; 9: 1995-2008. PMC4455953
Lau ME, Danka ES, Tiemann KM, Hunstad DA. Bacterial lysis liberates the neutrophil migration suppressor YbcL from the periplasm of uropathogenic Escherichia coli. Infect Immun 2014; 82: 4921-4930. PMC4249291
Lau ME, Loughman JA, Hunstad DA. YbcL of uropathogenic Escherichia coli suppresses transepithelial neutrophil migration. Infect Immun 2012; 80: 4123-4132. PMC3497442
Loughman JA, Hunstad DA. Induction of indoleamine 2,3-dioxygenase by uropathogenic bacteria attenuates innate responses to epithelial infection. J Infect Dis 2012; 205: 1830-1839. PMC3415894
Hunstad DA, Justice SS. Intracellular lifestyles and immune evasion strategies of uropathogenic Escherichia coli. Annu Rev Microbiol 2010 64: 203-221.
Nicholson TF, Watts KM, Hunstad DA. OmpA of uropathogenic Escherichia coli promotes post-invasion pathogenesis of cystitis. Infect Immun 2009 77: 5245-5251. PMC2786482
Last Updated: 8/24/2016 3:19:29 PM
Tubular inflammation, dropout and edema during severe Escherichia coli pyelonephritis in C3H/HeN male mice (Gomori trichrome stain).