Journal
SCIENCE ADVANCES
Volume 3, Issue 2, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.1601944
Keywords
-
Categories
Funding
- NIH National Institute of Allergy and Infectious Diseases (NIAID) [R01 AI029549, R01 AI048689, U01 AI095542]
- National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK051406]
- Medical Scientist Training Program through NIH [T32 GM07200]
- NIH NIAID [U01 AI095542]
- NIH National Institute for General Medical Sciences (NIGMS) [P41GM103422]
- NIH NIGMS [P41GM103422]
Ask authors/readers for more resources
Positive selection in the two-domain type 1 pilus adhesin FimH enhances Escherichia coli fitness in urinary tract infection (UTI). We report a comprehensive atomic-level view of FimH in two-state conformational ensembles in solution, composed of one low-affinity tense (T) and multiple high-affinity relaxed (R) conformations. Positively selected residues allosterically modulate the equilibrium between these two conformational states, each of which engages mannose through distinct binding orientations. A FimH variant that only adopts the R state is severely attenuated early in a mouse model of uncomplicated UTI but is proficient at colonizing catheterized bladders in vivo or bladder transitional-like epithelial cells in vitro. Thus, the bladder habitat has barrier(s) to R state-mediated colonization possibly conferred by the terminally differentiated bladder epithelium and/or decoy receptors in urine. Together, our studies reveal the conformational landscape in solution, binding mechanisms, and adhesive strength of an allosteric two-domain adhesin that evolved moderate affinity to optimize persistence in the bladder during UTI.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available