Date of Award

2012

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Microbiology and Immunology

Abstract

Urinary tract infections (UTI)s are a national priority. Women who undergo surgery for pelvic floor disorders such as pelvic organ prolapse (POP) or urinary incontinence (UI) are at increased risk for UTI, as 10-30% will contract a post-instrumentation UTI (postI-UTI) within six weeks after surgery. Currently, the factors that contribute to the high rate of postI-UTI are unknown, and there is currently no clinical assessment to identify at-risk patients. However, antimicrobial peptides (AMPs) and characteristics of the urinary microbiota have the potential to serve as biomarkers, identifying patients at UTI risk and facilitating clinical prevention studies.

While it was previously thought that the urinary tract was a sterile environment, new evidence shows that bacteria inhabit the urinary tract in many people. Given that microbial communities (microbiota) in other areas of the body exist in a balance with the host defense system, a similar equilibrium likely exists between the microbiota and host defenses in the urinary tract. AMPs, one significant component of our innate defense system, can limit pathogenic infection by their abilities to interact with and disrupt microbial membranes, and to stimulate immune cell recruitment. While it is reported that certain AMPs are expressed in the urinary tract, the AMP profile of the urinary tract has not been characterized. Inappropriate expression of AMPs in other tissues, including altered levels and/or activity, has been associated with several

different disease states. It is therefore possible that POP/UI surgery patients that express inappropriate AMP levels or decreased AMP potency have an imbalance between their defenses and their resident microbiota, which results in their susceptibility to postI-UTI.

These results begin to reveal the urinary antimicrobial peptide and microbiota profiles of three cohorts of patients: (1) POP/UI patients with culture-negative urine samples at baseline who DO NOT develop a postI-UTI (2) POP/UI patients with culture-negative urine at baseline who DO develop a postI-UTI, and (3) POP/UI patients with positive clinical cultures at baseline. While levels of two AMPs, psoriasin and human β-defensin-1, do not significantly differ between the cohorts, preliminary evidence suggests that a characteristic microbiota may exist in patients who develop infection. Furthermore, AMPs and the microbiota may directly influence one another. Levels of psoriasin are lower in patients with detectable E. coli in their urine than in patients with other types of infections. In addition to this correlation, the presence of certain genera of bacteria positively correlates with levels of psoriasin. This could indicate that some members of the microbiota, by affecting levels of AMPs, influence the susceptibility of the urinary tract to invading pathogens. By furthering our understanding of urinary AMPs and the urinary microbiota, we take an important step toward being able to identify POP/UI patients who are at high risk for postI-UTI, and toward developing new therapeutic options for preventing infection.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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