Inflammation-Induced Adhesin-Receptor Interaction Provides a Fitness Advantage to Uropathogenic E. coli during Chronic Infection.

TitleInflammation-Induced Adhesin-Receptor Interaction Provides a Fitness Advantage to Uropathogenic E. coli during Chronic Infection.
Publication TypeJournal Article
Year of Publication2016
AuthorsConover, M. S., S. Ruer, J. Taganna, V. Kalas, H. De Greve, J. S. Pinkner, K. W. Dodson, H. Remaut, and S. J. Hultgren
JournalCell Host Microbe
Volume20
Issue4
Pagination482-492
Date Published2016 Oct 12
ISSN1934-6069
KeywordsAdhesins, Escherichia coli, Animals, Bacterial Adhesion, Cystitis, Disease Models, Animal, Escherichia coli Infections, Escherichia coli Vaccines, Gene Deletion, Glucans, Host-Pathogen Interactions, Mice, Receptors, Cell Surface, Uropathogenic Escherichia coli, Virulence
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.

DOI10.1016/j.chom.2016.08.013
Alternate JournalCell Host Microbe
PubMed ID27667696
PubMed Central IDPMC5294914
Grant ListR01 DK108840 / DK / NIDDK NIH HHS / United States
R01 AI048689 / AI / NIAID NIH HHS / United States
P50 DK064540 / DK / NIDDK NIH HHS / United States
F32 DK101171 / DK / NIDDK NIH HHS / United States
R01 DK051406 / DK / NIDDK NIH HHS / United States
T32 AI007172 / AI / NIAID NIH HHS / United States
subject_category: 
Research group: