title: Advanced glycation end products facilitate bacterial adherence in urinary tract infection in diabetic mice.
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.
authors.affiliation: 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.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ozer
authors.affiliation: 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.
authors.forename: Cengiz Z
authors.initials: CZ
authors.lastname: Altuntas
authors.affiliation: 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.
authors.forename: Kenan
authors.initials: K
authors.lastname: Izgi
authors.affiliation: 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.
authors.forename: Fuat
authors.initials: F
authors.lastname: Bicer
authors.affiliation: 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.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hultgren
authors.affiliation: 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.
authors.forename: Guiming
authors.initials: G
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Firouz
authors.initials: F
authors.lastname: Daneshgari
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000382:microbiology*; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D014552:Urinary Tract Infections / Q000382:microbiology*; D056689:Uropathogenic Escherichia coli / Q000502:physiology*; D019459:Urothelium / Q000737:chemistry
chemical_list: D017127:Glycation End Products, Advanced; D037102:Lectins
keywords: Nε-(carboxyethyl)lysine; Nε-(carboxymethyl) lysine; enzyme-linked lectin assay; glycoprotein; lectin