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A strong interest of ours is to directly measure bacterial gene expression during human infections. Thus, we are determining the contribution to pathogenesis of the virulence genes found to be specifically upregulated in the human host during a UTI. Our hypothesis, that the virulence of a UPEC strain is the sum of its capacity for adherence, iron acquisition, toxin production, and specific metabolite transport, is supported by our measurements of global gene expression patterns of uropathogenic E. coli during UTI in women attending the University Health Service Clinic at the University of Michigan for the symptoms of cystitis. Having identified the most highly expressed virulence genes during UTI in humans, we are now focusing efforts on intervention and prevention directed toward these specific targets. During this study, we are determining the representative transcriptome for uropathogenic E. coli during urinary tract infection in humans; and determining the mechanism of pathogenesis for newly discovered virulence determinants upregulated in E. coli infecting women with urinary tract infection.
The Mobley lab performed an RNAseq study defining of the core transcriptome of 14 clinical isolates directly collected from women with UTI compared to growth in urine in vitro. We found that UPEC undergo a specific transcriptional program to infection that is conserved across all 14 strains that we studied. Furthermore, we found that in patient samples nearly 25% of the reads aligned with ribosomal subunits (Sintsova et al, 2019), indicating that the UPEC were replicating at an astonishingly rapid rate.
This hemagglutination assay demonstrates the ability of different clinical strains of uropathogenic E. coli to express fimbriae and bind red blood cells.
Credit: Drs. Allyson Shea and Arwen Frick-Cheng
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