Persistence of Uropathogenic Escherichia coli in the Face of Multiple Antibiotics

Abstract

Numerous antibiotics have proven to be effective at ameliorating the clinical symptoms of urinary tract infections (UTIs), but recurrent and chronic infections continue to plague many individuals. Most UTIs are caused by strains of uropathogenic Escherichia coli (UPEC), which can form both extra-and intracellular biofilm-like communities within the bladder. UPEC also persist inside host urothelial cells in a more quiescent state, sequestered within late endosomal compartments. Here, we tested a panel of 17 different antibiotics, representing seven distinct functional classes, for their effects on the survival of the reference UPEC isolate UTI89 within both biofilms and host bladder urothelial cells. All but one of the tested antibiotics prevented UTI89 growth in broth culture, and most were at least modestly effective against bacteria present within in vitro-grown biofilms. In contrast, only a few of the antibiotics, including nitrofurantoin and the fluoroquinolones ciprofloxacin and sparfloxacin, were able to eliminate intracellular bacteria in bladder cell culture-based assays. However, in a mouse UTI model system in which these antibiotics reached concentrations in the urine specimens that far exceeded minimal inhibitory doses, UPEC reservoirs in bladder tissues were not effectively eradicated. We conclude that the persistence of UPEC within the bladder, regardless of antibiotic treatments, is likely facilitated by a combination of biofilm formation, entry of UPEC into a quiescent or semiquiescent state within host cells, and the stalwart permeability barrier function associated with the bladder urothelium.

Atg16L1 deficiency confers protection from uropathogenic Escherichia coli infection in vivo

“…Traditional antibiotics are unable to penetrate bladder epithelial barriers, and therefore, bacteria sequestered in QIRs can survive long term in protected niches. In addition, antibiotic therapy itself risks driving the pathogens into quiescence (43). Targeting and eliminating the small but significant intracellular pool of bacteria may have substantial clinical benefits to combat refractory and recurrent UTIs.…”

Modulation of Escherichia coli biofilm growth by cell-free spent cultures from lactobacilli

“…Together with other virulence factors, their biofilm-forming capacity is of special importance for longer-term persistence and recurrence [1], as well as for catheter-associated infections [2][3][4][5]. Biofilm microorganisms are much more resistant to antibiotic treatments than plankton [3,6,7]. The problems caused by sessile bacteria require alternative approaches to biofilm control.…”

Phylogenetic Groups and Pathogenicity Island Markers in Escherichia coli Isolated From Children

“…Urinary tract infections (UTIs) are common in children around the world with chronic and recurrent infections resulting in a wide range of complications including end-stage kidney disease (1,2). UTI occurs in about 3 -5% of girls and 1% of boys, with most girls infected before 5 years; furthermore 60 -80% of girls acquire a second infection at 18 months old after the 1st UTI (3).…”