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Persistence of uropathogenic Escherichia coli in the face of multiple antibiotics.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2010 May; Vol. 54 (5), pp. 1855-63. Date of Electronic Publication: 2010 Mar 15. - Publication Year :
- 2010
-
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.
- Subjects :
- Animals
Biofilms growth & development
Cell Membrane Permeability physiology
Cells, Cultured
Drug Resistance, Bacterial
Endosomes microbiology
Escherichia coli growth & development
Escherichia coli Infections pathology
Female
Humans
Mice
Mice, Inbred CBA
Microbial Sensitivity Tests
Recurrence
Urinary Bladder cytology
Urinary Tract Infections pathology
Urothelium pathology
Anti-Bacterial Agents pharmacology
Biofilms drug effects
Escherichia coli drug effects
Escherichia coli Infections drug therapy
Urinary Tract Infections drug therapy
Urothelium microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-6596
- Volume :
- 54
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 20231390
- Full Text :
- https://doi.org/10.1128/AAC.00014-10