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J. Bacteriol. doi:10.1128/JB.01744-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Defining Genomic Islands and Uropathogen-Specific Genes in Uropathogenic Escherichia coli

Amanda L. Lloyd, David A. Rasko, and Harry L. T. Mobley*

Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA

* To whom correspondence should be addressed. Email: hmobley{at}med.umich.edu.


   Abstract

Uropathogenic Escherichia coli (UPEC) are responsible for the majority of uncomplicated urinary tract infections, which can present clinically as cystitis or pyelonephritis. UPEC strain CFT073, isolated from the blood of a patient with acute pyelonephritis, was most cytotoxic and most virulent in mice among our strain collection. Based on the genome sequence of CFT073, microarrays were utilized in comparative genomic hybridization (CGH) analysis of a panel of uropathogenic and fecal/commensal E. coli isolates. Genomic DNA from seven UPEC (three pyelonephritis, four cystitis) isolates and three fecal/commensal strains including K-12 MG1655 was hybridized to the CFT073 microarray. The CFT073 genome contains 5379 genes; CGH analysis revealed that 2820 (52.4%) of these genes were common to all 11 E. coli strains, yet only 173 UPEC-specific genes were found in all UPEC strains by CGH but in none of the fecal/commensal strains. When the sequence of three additional sequenced UPEC strains (UTI89, 536, F11) and a commensal strain (HS) were added to the analysis, 131 genes present in all UPEC strains but in no fecal/commensal strains were identified. Seven previously unrecognized genomic islands (>30 kb) were delineated by CGH in addition to the three known pathogenicity islands. These genomic islands comprise 672 of the 5231 kb (12.8%) genome, demonstrating the importance of horizontal transfer for UPEC and the mosaic structure of the genome. UPEC strains contain a greater number of iron acquisition systems than fecal/commensal strains, reflective of adaptation to the iron-limiting urinary tract environment. Each strain displayed distinct differences in the number and type of known virulence factors. The large number of hypothetical genes in the CFT073 genome, especially those shown to be UPEC-specific, strongly suggest that many urovirulence factors remain uncharacterized.




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