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ETD__Ahmet Ozer.pdf (3.36 MB)

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Increased Bacterial Adherence and Decreased Bacterial Clearance in Urinary Tract Infections with Diabetes Mellitus

Ozer, Ahmet
http://rave.ohiolink.edu/etdc/view?acc_num=case1376406476

Abstract Details

2013, Doctor of Philosophy, Case Western Reserve University, Genetics.
Diabetic individuals are more susceptible to infections, and urinary tract infections (UTI) are the most common infection type in women with diabetes mellitus (DM). Bacteria colonize tissues predominantly by binding to cell surface carbohydrates, which may change in DM and thereby alter susceptibility to infections. Also, innate immune responses are impaired in DM, which may affect the outcome of infection. Complete knowledge of bacterial adherence and clearance effectiveness in UTI in diabetics is lacking. The objectives of the studies comprising this thesis are to investigate two major events that occur in the course of UTI and impact the final outcome of this painful ailment: bacterial adherence, with its possible facilitation by advanced glycation end products (AGEs), and bacterial clearance efficiency, with an emphasis on neutrophil recruitment. Using a murine model of type 1 DM in vivo, we determined if AGE accumulation on uroepithelial surfaces contributes to increased adherence of uropathogenic Escherichia coli (UPEC) in UTI in DM mice relative to non-DM mice. Then we evaluated bacterial clearance efficiency and neutrophil recruitment to the bladder in relation to the expression of local cytokines macrophage inflammatory protein 2 (MIP-2), keratinocyte chemokine (KC), monocyte chemotactic protein 1 (MCP-1), and interleukin 6 (IL-6) during UPEC-induced UTI. Significantly higher levels of UPEC adherence and AGEs were detected in bladders of diabetic mice compared with controls, and AGEs were shown to bind to isolated type 1 fimbriae in vitro. Diabetic mice showed prolonged bacterial clearance during UTI. Neutrophil recruitment was delayed and diminished early after UPEC installation in both bladder tissue and urine of diabetic mice compared with controls. Expression of the chemokines at the transcriptional and protein levels in response to UTI was markedly impaired in diabetic mice. Our results show that AGEs accumulate on bladder urothelium during DM and may serve as bacterial adherence facilitators in UPEC-induced UTI. This new functional concept of AGEs can be subjected to an extended array of studies addressing host-pathogen interactions and new therapeutic targets in UTI in DM. Impaired bacterial clearance in diabetic mice may be partly due to the lower expression of cytokines in response to UTI, resulting in lower and postponed recruitment of neutrophils to the bladder.
Firouz Daneshgari, M.D. (Advisor)
Shawn McCandless, M.D. (Committee Chair)
Mitchell L. Drumm, Ph.D. (Committee Member)
Craig A. Hodges, Ph.D. (Committee Member)
Xiaoxia Li, Ph.D. (Committee Member)
179 p.
Genetics; Microbiology; Molecular Biology
Urinary tract infections; UTI; Diabetes Mellitus; DM; diabetic mice; Uropathogenic E coli; UPEC; innate immunity; bacterial adherence; bacterial clearance; advanced glycation end products; AGEs; MIP-2; KC; MCP-1; IL-6; chemokines; neutrophil recruitment

Recommended Citations

Citations

  • Ozer, A. (2013). Increased Bacterial Adherence and Decreased Bacterial Clearance in Urinary Tract Infections with Diabetes Mellitus [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1376406476

    APA Style (7th edition)

  • Ozer, Ahmet. Increased Bacterial Adherence and Decreased Bacterial Clearance in Urinary Tract Infections with Diabetes Mellitus. 2013. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1376406476.

    MLA Style (8th edition)

  • Ozer, Ahmet. "Increased Bacterial Adherence and Decreased Bacterial Clearance in Urinary Tract Infections with Diabetes Mellitus." Doctoral dissertation, Case Western Reserve University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=case1376406476

    Chicago Manual of Style (17th edition)

case1376406476
899
© 2013, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.