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Pathog Dis. 2015 Jul;73(5). pii: ftu004. doi: 10.1093/femspd/ftu004. Epub 2014 Dec 4.

Advanced glycation end products facilitate bacterial adherence in urinary tract infection in diabetic mice.

Author information

1
Urology Institute, University Hospitals Case Medical Center and Department of Urology, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, USA Department of Genetics & Genomic Sciences, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
2
Urology Institute, University Hospitals Case Medical Center and Department of Urology, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
3
Urology Institute, University Hospitals Case Medical Center and Department of Urology, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, USA Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44105, USA.
4
Department of Molecular Microbiology, Center for Women's Infectious Disease Research, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
5
Urology Institute, University Hospitals Case Medical Center and Department of Urology, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, USA fxd22@case.edu.

Abstract

Diabetic individuals have increased susceptibility to urinary tract infection (UTI), a common, painful condition. During diabetes mellitus, non-enzymatic reactions between reducing sugars and protein amine groups result in excessive production of advanced glycation end products (AGEs) that accumulate in tissues. Since bacteria adhere to cell surfaces by binding to carbohydrates, we hypothesized that adherence of bacteria to the bladder in diabetics may be enhanced by accumulation of AGEs on urothelial surface proteins. Using a murine model of UTI, we observed increased adherence of type 1 fimbriated uropathogenic Escherichia coli (UPEC) to the bladder in streptozotocin-induced diabetic female mice compared with age-matched controls, along with increased concentrations of two common AGEs in superficial urothelial cells from diabetic bladders. Several lectins with different specificities exhibited increased binding to urothelial homogenates from diabetic mice compared with controls, and two of those lectins also bound to AGEs. Furthermore, mannose-binding type 1 fimbriae isolated from UPEC bound to different AGEs, and UPEC adherence to the bladder in diabetic mice, were inhibited by pretreatment of mice with the AGE inhibitor pyridoxamine. These results strongly suggest a role for urothelial AGE accumulation in increased bacterial adherence during UTI in diabetes.

KEYWORDS:

Nε-(carboxyethyl)lysine; Nε-(carboxymethyl) lysine; enzyme-linked lectin assay; glycoprotein; lectin

PMID:
25986378
PMCID:
PMC4444075
DOI:
10.1093/femspd/ftu004
[Indexed for MEDLINE]
Free PMC Article

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