Impact of host age and parity on susceptibility to severe urinary tract infection in a murine model.

Kimberly A Kline,Drew J Schwartz,Amanda L Lewis,Nicole M Gilbert

doi:10.1371/journal.pone.0097798

Abstract

The epidemiology and bacteriology of urinary tract infection (UTI) varies across the human lifespan, but the reasons for these differences are poorly understood. Using established monomicrobial and polymicrobial murine UTI models caused by uropathogenic Escherichia coli (UPEC) and/or Group B Streptococcus (GBS), we demonstrate age and parity as inter-related factors contributing to UTI susceptibility. Young nulliparous animals exhibited 10–100-fold higher bacterial titers compared to older animals. In contrast, multiparity was associated with more severe acute cystitis in older animals compared to age-matched nulliparous controls, particularly in the context of polymicrobial infection where UPEC titers were ∼1000-fold higher in the multiparous compared to the nulliparous host. Multiparity was also associated with significantly increased risk of chronic high titer UPEC cystitis and ascending pyelonephritis. Further evidence is provided that the increased UPEC load in multiparous animals required TLR4-signaling. Together, these data strongly suggest that the experience of childbearing fundamentally and permanently changes the urinary tract and its response to pathogens in a manner that increases susceptibility to severe UTI. Moreover, this murine model provides a system for dissecting these and other lifespan-associated risk factors contributing to severe UTI in at-risk groups.

Highlights

Urinary tract infection (UTI) is one of the most common bacterial infections in humans, with an estimated annual incidence rate of nearly 13% in women [1]
We showed that Group B Streptococcus (GBS) presence along with uropathogenic Escherichia coli (UPEC) at the time of inoculation significantly altered acute and chronic UPEC UTI outcomes, despite the fact that GBS was rapidly cleared from the urinary tract within the first 24 hours after infection [3]
These experiments showed that young nulliparous mice experienced more severe acute cystitis compared to aged nulliparous mice at 24 hours post infection (,100-fold higher bladder titers of UPEC and,15-fold higher GBS titers in young vs. aged nulliparous mice) (Fig. 1A–B)

Summary

Introduction

Urinary tract infection (UTI) is one of the most common bacterial infections in humans, with an estimated annual incidence rate of nearly 13% in women [1]. Uncomplicated UTI are most often caused by uropathogenic Escherichia coli (UPEC). Complicated UTI is associated with functional or structural urinary tract abnormalities, pregnancy, or urinary catheterization. These host factors are associated with increased rates of infection with a more diverse array of organisms, including Streptococcus agalactiae (Group B Streptococcus, GBS). GBS commonly colonizes the same anatomical niches (urogenital tract, gut) as UPEC, is adept at causing infections in a variety of human tissues including the urinary tract, and has immune modulatory capabilities [3,4,5]

Methods

Results

Conclusion