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Inflammation-induced adhesin-receptor interaction provides a fitness advantage to uropathogenic E. coli during chronic infection

DOI: 10.1016/j.chom.2016.08.013 DOI Help

Authors: Matt s. Conover (Washington University School of Medicine) , Ségolène Ruer (Structural Biology Research Center, VIB; Vrije Universiteit Brussel) , Joemar Taganna (Structural Biology Research Center, VIB; Vrije Universiteit Brussel) , Vasilios Kalas (Washington University School of Medicine) , Henri De greve (Structural Biology Research Center, VIB; Vrije Universiteit Brussel) , Jerome s. Pinkner (Washington University School of Medicine) , Karen w. Dodson (Washington University School of Medicine) , Han Remaut (Structural Biology Research Center, VIB; Vrije Universiteit Brussel) , Scott j. Hultgren (Washington University School of Medicine)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell Host & Microbe , VOL 20 , PAGES 482 - 492

State: Published (Approved)
Published: October 2016
Diamond Proposal Number(s): 7351 , 12718

Abstract: Uropathogenic E. coli (UPEC) is the dominant cause of urinary tract infections, clinically described as cystitis. UPEC express CUP pili, which are extracellular fibers tipped with adhesins that bind mucosal surfaces of the urinary tract. Here we identify the role of the F9/Yde/Fml pilus for UPEC persistence in the inflamed urothelium. The Fml adhesin FmlH binds galactose β1-3 N-acetylgalactosamine found in core-1 and -2 O-glycans. Deletion of fmlH had no effect on UPEC virulence in an acute mouse model of cystitis. However, FmlH provided a fitness advantage during chronic cystitis, which is manifested as persistent bacteriuria, high bladder bacterial burdens, and chronic inflammation. In situ binding confirmed that FmlH bound avidly to the inflamed, but not the naive bladder. In accordance with its pathogenic profile, vaccination with FmlH significantly protected mice from chronic cystitis. Thus, UPEC employ separate CUP pili to adapt to the rapidly changing niche during bladder infection.

Diamond Keywords: Bacteria

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I04-Macromolecular Crystallography

Added On: 23/11/2016 13:03

Discipline Tags:

Vaccines Pathogens Antibiotic Resistance Infectious Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)