Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli

Abstract

We present the complete genome sequence of uropathogenic Escherichia coli, strain CFT073. A three-way genome comparison of the CFT073, enterohemorrhagic E. coli EDL933, and laboratory strain MG1655 reveals that, amazingly, only 39.2% of their combined (nonredundant) set of proteins actually are common to all three strains. The pathogen genomes are as different from each other as each pathogen is from the benign strain. The difference in disease potential between O157:H7 and CFT073 is reflected in the absence of genes for type III secretion system or phage- and plasmid-encoded toxins found in some classes of diarrheagenic E. coli. The CFT073 genome is particularly rich in genes that encode potential fimbrial adhesins, autotransporters, iron-sequestration systems, and phase-switch recombinases. Striking differences exist between the large pathogenicity islands of CFT073 and two other well-studied uropathogenic E. coli strains, J96 and 536. Comparisons indicate that extraintestinal pathogenic E. coli arose independently from multiple clonal lineages. The different E. coli pathotypes have maintained a remarkable synteny of common, vertically evolved genes, whereas many islands interrupting this common backbone have been acquired by different horizontal transfer events in each strain.

Fig 1.

Map of the CFT073 genome and comparison with K-12 strain MG1655. The outer circle shows ORFs, colored according to the K-12 comparison in the second circle, where DNA regions are shown: blue, backbone, i.e., E. coli near match to MG1655; red, CFT073 islands (insertions); orange, islands (substitutions replacing K-12 segments); violet, K-12 islands. ORFs in the outer ring that span island–backbone junctions are pink. Third circle, RNAs: green, rRNA operons; blue, tRNAs; gold, miscellaneous RNAs. Fourth circle, scale in bp. Fifth circle, GC skew calculated for each ORF >100 aa, colored according to the same scheme of the ORF circle and plotted around the mean. Sixth circle, GC skew calculated over the whole sequence (window, 10 kb) plotted around the mean. Seventh circle, codon-adaptation index CAI (inverse, 1-CAI is plotted); pink rays indicate CAI values <0.2; purple rays, values >0.2. The pink rays can be seen to correspond with islands. A detailed linear map with ORF annotations is available at www.genome.wisc.edu. Maps were created by GENVISION from DNASTAR.

Fig 2.

Shared E. coli proteins. Comparison of the predicted proteins of the three E. coli strains shows the number of orthologs in each shared category and numbers of strain-specific proteins. Hypervariable proteins and proteins spanning island–backbone junctions were excluded from the analysis. Number of proteins counted: K-12, 4,288; CFT073, 5,016; EDL933, 5,063. In the totals for the three strains, orthologous proteins are counted only once. Orthologous proteins meet the same match criteria used for designation of backbone (see Materials and Methods).

Fig 3.

Locations and sizes of CFT073 and EDL933 islands. Island size, vertical axis; position in colinear backbone, horizontal axis. All islands >4 kb are shown. Islands located at tRNAs are indicated by tRNA labels. One tmRNA (ssrA) is also an insertion target. *, CFT073 and EDL933 islands in the same backbone location but not near tRNAs.