Study sheds new light on urinary tract infections in postmenopausal women

UT Southwestern Medical Center

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DALLAS – May
12, 2019 – A UT Southwestern study suggests why urinary tract
infections
(UTIs) have such a high recurrence rate in
postmenopausal women – several species of bacteria can invade the
bladder walls.

Recurrent
UTI (RUTI) reduces quality of life

UTI
treatment is the most common reason for antibiotic prescriptions in older
adults. Because of the prevalence of UTIs, the societal impact is high and
treatment costs billions of dollars annually.

“Recurrent
UTI (RUTI) reduces quality of life, places a significant burden on the health
care system, and contributes to antimicrobial resistance,” said Dr. Kim Orth,
Professor of Molecular Biology and Biochemistry at UTSW and senior author of
the study, published in the Journal of Molecular Biology.

The
investigation demonstrates that several species of bacteria can work their way
inside the human bladder’s surface area, called the urothelium, in RUTI
patients. Bacterial diversity, antibiotic resistance, and the
adaptive immune response all play important roles in this disease, the study
suggests.

“Our findings
represent a step in understanding RUTIs in postmenopausal women,” said Dr.
Orth, also an Investigator of the prestigious Howard Hughes Medical Institute
who holds the Earl A. Forsythe Chair in Biomedical Science and is a W.W.
Caruth, Jr. Scholar in Biomedical Research at UTSW. “We will need to use
methods other than antibiotics to treat this disease, as now we observe diverse
types of bacteria in the bladder wall of these patients.”

Since the advent of antibiotics in the 1950s, patients and physicians have relied on antibiotics for UTI treatment.

“As time
went on, however, major antibiotic allergy and resistance issues have emerged,
leading to very challenging and complex situations for which few treatment
choices are left and one’s life can be on the line,” said Dr. Philippe Zimmern,
Professor of Urology and a co-senior author. “Therefore, this new body
of data in women affected by RUTIs exemplifies what a multidisciplinary
collaboration can achieve going back and forth between the laboratory and the
clinic.”

UTIs are one
of the most common types of bacterial infections in women,
accounting for nearly 25 percent of all infections. Recurrence can range from
16-36 percent in premenopausal women to 55 percent following menopause. Factors
thought to drive higher UTI rates in postmenopausal women include pelvic organ
prolapse, diabetes, lack of estrogen, loss of Lactobacilli in the vaginal
flora, and increased colonization of tissues surrounding the urethra by
Escherichia coli (E. coli).

The latest
findings build on decades of clinical UTI discoveries by Dr. Zimmern, who
suggested the collaboration to Dr. Orth, along with other UT System colleagues.

The UTSW
team, which included researchers from Molecular Biology, Pathology,
Urology, and Biochemistry,
examined bacteria in bladder biopsies from
14 RUTI patients using targeted fluorescent markers, a technique that had not
been used to look for bacteria in human bladder tissue.

“The
bacteria we observed are able to infiltrate deep into the bladder wall tissue,
even past the urothelium layer,” said first and co-corresponding author Dr.
Nicole De Nisco, an Assistant Professor of Biological Sciences at UT Dallas who
initiated this research as a postdoctoral fellow in Dr. Orth’s lab. “We also
found that the adaptive immune response is quite active in human RUTIs.”

Accessing
human tissue was key, the researchers note, as the field has largely relied on
mouse models that are limited to lifespans of 1.3 to 3 years, depending on the
breed.

“Most of the
work in the literature has dealt with women age 25 to 40,” said Dr. Zimmern,
who holds The Felecia and John Cain Chair in Women’s Health, recently
established in his honor. “This is direct evidence in postmenopausal women
affected with RUTIs, a segment of our population that has grown with the aging
of baby boomers and longer life expectancy in women.”

Future
studies will focus on determining effective techniques to remove these bacteria
and chronic inflammation from the bladder, finding new strategies to enhance immune
system response, and pinpointing the various bacterial pathogens involved in
RUTIs.

Other team
members from UTSW include Dr. Marcela de Souza Santos, former Assistant
Professor of Molecular Biology; Dr. Jason Mull, former Assistant Professor of
Pathology; Luming Chen, a graduate student researcher in the Medical Scientist
Training Program; and Inkkaruch Kuprasertkul, a medical student who worked on
the investigation as part of her summer research project. Dr. Kelli Palmer,
Associate Professor of Biological Sciences at UTD and Cecil H. and Ida Green
Chair in Systems Biology Science Fellow, and Michael Neugent, UTD doctoral
candidate, also contributed.

The study was funded by the National Institutes of Health (NIH), The Welch Foundation, Once Upon a Time …, and the Cecil H. and Ida Green Chair in Systems Biology Science.

About UT
Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the USA, integrates pioneering biomedical research with exceptional clinical care and education.




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