April 3, 2010 at 5:47 pm #2855
Friday, 02 April 2010
Division of Cell Biology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah 84112.
Numerous antibiotics are proven 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 of 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 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 that far exceeded minimal inhibitory doses, UPEC reservoirs in bladder tissues were not effectively eradicated. We conclude that 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 semi-quiescent state within host cells, and the stalwart permeability barrier function associated with the bladder urothelium.
Blango MG, Mulvey MA.
Antimicrob Agents Chemother. 2010 Mar 15. Epub ahead of print.
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