Combined functional genomic and metabolomic approaches identify new genes required for growth in human urine by multidrug resistant Escherichia coli ST131

UPEC cause ~80% of all UTIs, with increasing rates of antibiotic resistance presenting an urgent threat to effective treatment. To cause infection UPEC must grow efficiently in human urine (HU), necessitating a need to understand mechanisms that promote its adaptation and survival in this nutrient-limited environment. Here, we used a combination of functional genomic and metabolomic techniques and identified roles for the metabolism of small peptides, amino acids, nucleotides and L-lactate, as well as the stringent response pathway, LPS biosynthesis and fluoride resistance, for UPEC growth in HU. We further demonstrated pathways involving nucleotide metabolism and the stringent response are required for UPEC colonization of the mouse bladder. The UPEC genes and metabolic pathways identified in this study represent targets for the development of innovative therapeutics to prevent UPEC growth during human UTI, an urgent need given the rapidly rising rates of global antibiotic resistance.The data submitted in this BioProject is from the TraDIS experiment involving growth of UPEC strain EC958 in HU.