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Infection and Immunity, November 2004, p. 6373-6381, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6373-6381.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Transcriptome of Uropathogenic Escherichia coli during Urinary Tract Infection

Jennifer A. Snyder,1 Brian J. Haugen,2 Eric L. Buckles,3 C. Virginia Lockatell,3 David E. Johnson,3,4 Michael S. Donnenberg,3 Rodney A. Welch,2 and Harry L. T. Mobley1*

Department of Microbiology and Immunology,1 Division of Infectious Diseases, University of Maryland School of Medicine,3 Department of Veterans Affairs, Baltimore, Maryland,4 Department of Medical Microbiology and Immunology, University of Wisconsin—Madison, Madison, Wisconsin2

Received 11 June 2004/ Returned for modification 14 July 2004/ Accepted 29 July 2004

A uropathogenic Escherichia coli strain CFT073-specific DNA microarray that includes each open reading frame was used to analyze the transcriptome of CFT073 bacteria isolated directly from the urine of infected CBA/J mice. The in vivo expression profiles were compared to that of E. coli CFT073 grown statically to exponential phase in rich medium, revealing the strategies this pathogen uses in vivo for colonization, growth, and survival in the urinary tract environment. The most highly expressed genes overall in vivo encoded translational machinery, indicating that the bacteria were in a rapid growth state despite specific nutrient limitations. Expression of type 1 fimbriae, a virulence factor involved in adherence, was highly upregulated in vivo. Five iron acquisition systems were all highly upregulated during urinary tract infection, as were genes responsible for capsular polysaccharide and lipopolysaccharide synthesis, drug resistance, and microcin secretion. Surprisingly, other fimbrial genes, such as pap and foc/sfa, and genes involved in motility and chemotaxis were downregulated in vivo. E. coli CFT073 grown in human urine resulted in the upregulation of iron acquisition, capsule, and microcin secretion genes, thus partially mimicking growth in vivo. On the basis of gene expression levels, the urinary tract appears to be nitrogen and iron limiting, of high osmolarity, and of moderate oxygenation. This study represents the first assessment of any E. coli pathotype's transcriptome in vivo and provides specific insights into the mechanisms necessary for urinary tract pathogenesis.


* Corresponding author. Present address: Department of Microbiology and Immunology, University of Michigan Medical School, 5641 Medical Science Building II, 1150 West Medical Center Dr., Ann Arbor, MI 48109. Phone: (734) 763-3531. Fax: (734) 764-3562. E-mail: hmobley{at}med.umich.edu.

Editor: A. D. O'Brien


Infection and Immunity, November 2004, p. 6373-6381, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6373-6381.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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