Transcriptome of uropathogenic Escherichia coli during urinary tract infection

Abstract

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.

FIG. 1.

Functional categories of differentially expressed E. coli CFT073 genes. The number of genes that are significantly upregulated (black bars) or downregulated (grey bars) during growth in vivo (growth during UTI) relative to growth in static LB culture are categorized based on function.

FIG. 2.

Expression of adhesins in E. coli CFT073. The signal intensity, corresponding to the relative expression of a gene, is shown for selected adhesin genes in vivo (growth during UTI) or in vitro (growth in static LB culture). Genes upregulated (encircled plus signs) or downregulated (encircled minus signs) in vivo relative to in vitro are indicated.

FIG. 3.

Expression of iron acquisition systems in E. coli CFT073. The signal intensity, corresponding to the relative expression of a gene, is shown for selected iron acquisition systems in vivo (growth during UTI) or in vitro (growth in static LB culture). Genes upregulated (encircled plus signs) in vivo relative to the same genes in vitro are indicated.