Presentation Authors: Anna Sintsova*, Ali Pirani, Ann Arbor, MI, Sargurunathan Subashchandrabose, Winston-Salem, NC, Evan Snitkin, Harry L.T. Mobley, Ann Arbor, MI
Introduction: Uropathogenic Escherichia coli (UPEC) is the major causative agent of uncomplicated urinary tract infections (UTIs). UPEC strains carry diverse assortments of virulence factors and a common virulence genotype responsible for urinary tract infection is yet to be defined. We hypothesized that studying patterns of gene expression in patients might identify universal bacterial features that enable uropathogenesis.
Methods: Using RNA sequencing technology, we examined UPEC gene expression directly in 14 patients presenting with uncomplicated UTI and compared it to the gene expression of identical strains cultured in vitro to mid-exponential stage in filter-sterilized human urine.
Results: Here we identify a common transcriptional program shared by genetically diverse UPEC strains isolated from 14 patients with uncomplicated UTIs. Strikingly, the conserved gene expression program in patients is distinct from one observed during in vitro urine culture of the identical strains. Moreover, regulatory network analysis reveals that drastic downregulation of key metabolic regulons in all 14 UPEC strains facilitates markedly increased expression of translation and replication machinery.
Conclusions: Taken together, our study identifies for the first time a common thread underlying UTI and illuminates the molecular underpinnings that likely facilitate the remarkably fast growth rate of UPEC that has been previously observed in infected patients.
Source of Funding: AUA Fellowship, NIH award number R01 DK094777