TY - JOUR
T1 - Inflammation-Induced Adhesin-Receptor Interaction Provides a Fitness Advantage to Uropathogenic E. coli during Chronic Infection
AU - Conover, Matt S.
AU - Ruer, Ségolène
AU - Taganna, Joemar
AU - Kalas, Vasilios
AU - De Greve, Henri
AU - Pinkner, Jerome S.
AU - Dodson, Karen W.
AU - Remaut, Han
AU - Hultgren, Scott J.
N1 - Funding Information:
We would like to acknowledge Nathaniel Gualberto for his cloning expertise and Tam Mignot for the gift of the pSWU19 plasmid. We would also like to thank Danielle Liu and Mike Hibbing for their assistance with mouse experiments. We acknowledge the kind support of beamline staff at PROXIMA1 - SOLEIL and i04 - Diamond Light Source, as well as the participation of the Protein-Glycan Interaction Resource of the CFG. This work was funded through S.J.H., P50 DK064540, R01 DK051406, and R01 AI048689; M.C., F32 DK101171-02; H.R., G030411N (FWO) and UABR/09/005 (Hercules foundation). S.J.H. has a financial ownership in Fimbrion and may financially benefit if the company is successful in marketing the mannosides related to this research and may receive royalty income based on the FimH vaccine technology that he developed which was licensed by Washington University to Sequoia Sciences.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/10/12
Y1 - 2016/10/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84992415770&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2016.08.013
DO - 10.1016/j.chom.2016.08.013
M3 - Article
C2 - 27667696
AN - SCOPUS:84992415770
SN - 1931-3128
VL - 20
SP - 482
EP - 492
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 4
ER -