title: Uropathogenic Escherichia coli induces serum amyloid a in mice following urinary tract and systemic inoculation.
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.
authors.affiliation: Faculty of Medicine, Institute of Cell Biology, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Andreja
authors.initials: A
authors.lastname: Erman
authors.forename: Katja
authors.initials: K
authors.lastname: Lakota
authors.forename: Katjusa
authors.initials: K
authors.lastname: Mrak-Poljsak
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Blango
authors.forename: Veronika
authors.initials: V
authors.lastname: Krizan-Hergouth
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Mulvey
authors.forename: Snezna
authors.initials: S
authors.lastname: Sodin-Semrl
authors.forename: Peter
authors.initials: P
authors.lastname: Veranic
mesh_terms: D000818:Animals; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D060888:Real-Time Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000378:metabolism* / Q000494:pharmacology; D014552:Urinary Tract Infections / Q000378:metabolism* / Q000382:microbiology; D056689:Uropathogenic Escherichia coli / Q000187:drug effects / Q000472:pathogenicity*
chemical_list: D000685:Serum Amyloid A Protein