Scott J. Hultgren

What they work on

1. Determine how shape changes in bacterial adhesins control attachment, comparing FimH of uropathogenic E. coli and Klebsiella, the pectin-binding YehD and the fibrinogen-binding Abp2D of Acinetobacter using structural biology, molecular dynamics and biochemistry.
2. Design small de novo proteins under 20 kDa and engineered monoclonal antibodies, using deep learning and protein structure prediction, that block host-pathogen contacts in UPEC, Klebsiella, Acinetobacter, Enterococcus and Staphylococcus.
3. Develop glycomimetics and antibodies that neutralize chaperone usher pathway pili and GmPcides, ring-fused 2-pyridone compounds active against Gram-positive pathogens, and test leads in mouse UTI, catheter-associated UTI and skin infection models.
4. Test whether a prior bladder infection leaves epigenetic marks on bladder epithelial stem cells that change expression of programmed cell death genes, tumor necrosis factor alpha and cyclooxygenase-2 and raise susceptibility to reinfection.
5. Ask how adaptive immunity shapes recurrence by depleting CD4+ and CD8+ T cells in mice and tracking susceptibility to reinfection with the same E. coli strain.
6. Identify how gut mucus, the microbial community and interleukin-22 with its binding protein restrict UPEC colonization of the intestine in health and after antibiotic-driven disturbance.
7. Characterize the distinct gene-expression state of E. coli in the disturbed gut of women with recurrent UTI and test whether bacteria in that state colonize the mouse bladder more efficiently.
8. Assess whether vaginal and periurethral microbial communities promote or block E. coli transit to the bladder, as intermediate reservoirs on the way to infection.
9. Profile mixed-species communities and resistance genes on long-term urinary catheters and stents by third-generation metagenomic sequencing within seven hours of sampling, and link specific members to patients' symptoms.
10. Test whether therapeutics effective against single uropathogens also clear mixed-species catheter infections, using mouse CAUTI and laboratory biofilm models of bacterial-bacterial interactions.

More about the research

Why it matters

Antibiotic resistance is already making some everyday infections hard to treat. By blocking the proteins bacteria use to grab onto bladder tissue and catheters instead of killing them outright, this work could yield treatments that work against drug-resistant strains while reducing the antibiotic use that breeds resistance. Rapid sequencing of catheter infections could let clinicians choose the right drug the same day, and insight into why infections recur may help the millions of women with repeated UTIs.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

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The school

Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.

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