Genetically diverse uropathogenic Escherichia coli adopt a common transcriptional program in patients with UTIs

Abstract

Uropathogenic Escherichia coli (UPEC) is the major causative agent of uncomplicated urinary tract infections (UTIs). A common virulence genotype of UPEC strains responsible for UTIs is yet to be defined, due to the large variation of virulence factors observed in UPEC strains. We hypothesized that studying UPEC functional responses in patients might reveal universal UPEC features that enable pathogenesis. Here we identify a transcriptional program shared by genetically diverse UPEC strains isolated from 14 patients during uncomplicated UTIs. Strikingly, this in vivo gene expression program is marked by upregulation of translational machinery, providing a mechanism for the rapid growth within the host. Our analysis indicates that switching to a more specialized catabolism and scavenging lifestyle in the host allows for the increased translational output. Our study identifies a common transcriptional program underlying UTIs and illuminates the molecular underpinnings that likely facilitate the fast growth rate of UPEC in infected patients.

The Gene Expression Profile of UropathogenicEscherichia coliin Women with Uncomplicated Urinary Tract Infections Is Recapitulated in the Mouse Model

“…In contrast, the in vitro human urine culture when compared to hUTI exhibited lower correlation values of 0.73-0.80 ( Fig. 3) , consistent with our previous report (13). Interestingly, gene expression correlation between LB and hUTI was higher than the correlation between urine and hUTI ( r between 0.80-0.88) ( Fig 3 ).…”

“…We previously sequenced the transcriptomes of 14 UPEC strains isolated directly from the urine of patients with uncomplicated UTIs (hUTI) and immediately stabilized with RNAprotect (13). Three out of 14 strains (HM43, HM56, and HM86) were chosen to conduct transcriptomic studies in the prevailing mouse model of UTI (mUTI) (8).…”

“…We selected strains whose hUTI transcriptomes had the highest proportion of bacterial reads to eukaryotic reads ( Supplemental Table 1 ) and that possessed a prototypical UPEC virulence factor profile. All three strains belong to the B2 phylogroup (13), where the majority of UPEC strains reside, and encode a range of siderophores, heme receptors, as well as multiple fimbrial types ( Fig. 1 ).…”

“…We have recently shown that diverse UPEC strains show a conserved gene expression pattern in human patients with uncomplicated UTIs (13). Since we saw such strong correlation between gene expression in patients and in mice for each of the UPEC strains ( Fig 3) , we hypothesized that we would also observe a conserved pattern of gene expression between different UPEC strains during mUTI.…”

Optimization of an Experimental Vaccine to PreventEscherichia coliUrinary Tract Infection

“…Furthermore, IutA has been shown to be highly expressed in the mouse model of ascending UTI, as assessed by RNA microarray, and in women presenting with symptoms of cystitis (32, 75, 76). Indeed, RNAseq data from 14 different strains, stabilized immediately following urine collection, clearly demonstrated that iutA, hma, fyuA , and ireA , are highly expressed in vivo in women with acute cystitis (77). Based on its efficacy and antigenicity, IutA should be considered for inclusion in future UTI vaccines, particularly those aimed at increasing the breadth of protection against UPEC strains and overcoming the functional redundancy of iron receptors by incorporation of multiple antigens.…”