Uropathogenic Escherichia coli Induces Serum Amyloid A in Mice following Urinary Tract and Systemic Inoculation

Andreja Erman,Matthew A Mulvey,Katja Lakota,Katjusa Mrak-Poljsak,Matthew G Blango,Snezna Sodin-Semrl,Peter Veranic,Veronika Krizan-Hergouth,Adam J Ratner

doi:10.1371/journal.pone.0032933

Andreja Erman, Matthew A Mulvey + Show 7 more

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https://doi.org/10.1371/journal.pone.0032933

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Abstract

Serum amyloid A (SAA) is an acute phase protein involved in the homeostasis of inflammatory responses and appears to be a vital host defense component with protective anti-infective properties. SAA expression remains poorly defined in many tissues, including the urinary tract which often faces bacterial challenge. Urinary tract infections (UTIs) are usually caused by strains of uropathogenic Escherichia coli (UPEC) and frequently occur among otherwise healthy individuals, many of whom experience bouts of recurrent and relapsing infections despite the use of antibiotics. To date, whether SAA is present in the infected urothelium and whether or not the induction of SAA can protect the host against UPEC is unclear. Here we show, using mouse models coupled with immunofluorescence microscopy and quantitative RT-PCR, that delivery of UPEC either directly into the urinary tract via catheterization or systemically via intraperitoneal injection triggers the expression of SAA. As measured by ELISA, serum levels of SAA1/2 were also transiently elevated in response to UTI, but circulating SAA3 levels were only up-regulated substantially following intraperitoneal inoculation of UPEC. In in vitro assays, physiological relevant levels of SAA1/2 did not affect the growth or viability of UPEC, but were able to block biofilm formation by the uropathogens. We suggest that SAA functions as a critical host defense against UTIs, preventing the formation of biofilms both upon and within the urothelium and possibly providing clinicians with a sensitive serological marker for UTI.

Highlights

Upon entering the urinary tract, strains of uropathogenic Escherichia coli (UPEC) face a barage of both constitutive and inducible host defenses
At 1 and 4 d following catheterization of adult female C57BL/6JOLaHsd mice with the UPEC isolate UTI89, levels of SAA1/2 in the urothelium were observed to be notably elevated relative to uninfected controls (Fig. 1A–C)
In control experiments in which mice were infected systemically with UTI89 delivered via intraperitoneal (IP) injection, SAA3 expression was markedly increased in the liver as well as in the urothelium (,20-fold) and bladder wall (,90-fold)

Summary

Introduction

Upon entering the urinary tract, strains of uropathogenic Escherichia coli (UPEC) face a barage of both constitutive and inducible host defenses. Despite this hostile environment, which often includes the presence of antibiotics, UPEC is frequently able to establish itself within the host, multiply, and persist for many days to months. Persistence of UPEC within the bladder is in part attributable to the ability of these pathogens to invade urothelial cells where they can either multiply, forming large biofilm-like communities, or alternatively establish latent resevoirs which may lead to episodes of recurrent or relapsing urinary tract infections (UTIs) [1,2]. Preferential binding of SAA to OmpA over endogenous host ligands, including high density lipoprotein (HDL) [4], may significantly impact both the host environment and pathogen fitness during the course of an infection

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