CGH analysis provides a powerful tool for studying the prevalence of genes associated with genomic islands (GIs). The CFT073 genome was included in the design of our microarray and thus acted as an excellent reference for comparison of the UTI isolates. The GIs of the highly virulent pyelonephritis strain CFT073 are very well characterized (28
). In order to study the prevalence of CFT073-associated GIs among the UTI isolates, the genomic profiles of the isolates were compared with CFT073 with respect to CFT073-associated probes. A permissive cutoff value for the presence of an island (≥2/3 of the genes in an island predicted to be present) was selected to allow for some cross-hybridization between generic island elements, e.g., transposases and integrases (summarized in Tables 2
). Furthermore, the genomic profiles were analyzed with the GeneWiz BLAST atlas program, which was used to compare the inferred genomic profile of each UTI isolate to the genomic sequence of CFT073 (Fig. 2
). The UTI isolates were compared with respect to disease category, as well as phylogenetic group association.
Several of the GIs, including PAI-CFT073-icdA
, and PAI-CFT073-pheU
and Fig. 2
), were found to be significantly more associated with the urosepsis and pyelonephritis isolates than with the cystitis and ABU isolates, suggesting that these islands are associated with highly virulent UPEC strains. However, the majority of these islands were also significantly linked to the phylogenetic group origin (Table 3
). Separate analysis of the B2 isolates revealed a significantly greater prevalence of PAI-CFT073-serU
among the urosepsis and pyelonephritis isolates than among the cystitis and ABU isolates (Table 3
). One island, viz.
, or the high-pathogenicity island (HPI), was found in all B2 isolates. Arguably, this suggests that the island was acquired early in the evolution of the lineage (Table 3
). Most sequenced B2 strains, including the two commensal isolates SE15 and ED1a, also carry this island. However, the HPI is not restricted to group B2; it was found, in particular, among the group D isolates and in one of the two group A isolates. Another island, PAI-CFT073-metV
, was also present in all but one of the group B2 isolates (cystitis isolate VR158). PAI-CFT073-metV
has previously been shown to contribute to upper urinary tract infection (in a mouse model), an activity shown to be associated with the last six genes in the island (28
). In fact, although VR158 was predicted to lack the majority of the island (resulting in an overall absence call), the strain contained five of these genes (c3405
was not on the microarray). The B2 commensal strain SE15 also carries this island, and the other B2 commensal strain, ED1a, carries the last six genes. Several islands were found exclusively among the B2 UTI strains (as compared to the sequenced non-UTI strains [see Fig. S3 in the supplemental material]), i.e., PAI-CFT073-aspV
, and GI-CFT073-leuX
. Two PAIs, PAI-CFT073-asnT
, were particularly prevalent among the group D strains (Table 3
). The group A strains had very few islands; only two islands were predicted to be present, i.e., PAI-CFT073-asnT
in ABU strain VR95 and GI-CFT073-cobU
in cystitis strain VR148. Although these strains may carry other non-CFT073-like islands, it is possible that these islands contribute to persistence in the urinary tract.
Although the majority of the PAIs (63%) were more commonly associated with the urosepsis and pyelonephritis isolates than with the cystitis and ABU strains, a considerable fraction of the cystitis and ABU isolates contained multiple PAIs, and none of these strains were completely devoid of genes from these PAIs (Table 2
). The average number of GIs per strain decreased according to the severity of the infection caused by the strain; urosepsis, pyelonephritis, cystitis, and ABU strains carried on average 8.1, 6.4, 4.4, and 4.1 GIs per strain, respectively. However, there was no significant difference between the different disease categories within the same phylogenetic group; in the B2 group, which contained strains from all four disease categories, the urosepsis, pyelonephritis, cystitis, and ABU isolates carried on average 8.1, 8.6, 6.3, and 7.4 islands, respectively. On the other hand, the two commensal strains in the B2 group contained only 3.5 GIs per strain (Table 3
). The average number of islands present per strain from each phylogenetic group was 7.8, 3.6, 1.3, and 1.0 for groups B2, D, B1, and A, respectively. Altogether, although the number of GIs is significantly higher in a UTI strain than in a commensal strain, our results suggest that the number of GIs present in a UTI strain is linked to the phylogenetic group association rather than to the disease category.