Characterization of pyelonephritis and cystitis E. coli isolates – Comparison of bacterial traits involved in colonization of the lower or upper urinary tract

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Uropathogenic Escherichia coli (UPEC) are the most common pathogens of lower and upper urinary tract infections (UTIs). Kidneys and urinary bladders differ significantly, among other things, anatomically and in terms of an immune response. We assume that UPEC adapt to the respective environment which profoundly differs between kidney and bladder, e.g., in terms of tonicity and nutrient availability. There is also epidemiological evidence that pyelonephritis and cystitis isolates differ. We hypothesize that UPEC employ different adaptation strategies during upper and lower UTI. We will perform comparative genomics on pyelonephritis and cystitis isolates to identify bacterial factors that determine pathogenicity in the kidneys and bladder, respectively. Using selected virulence factors and small regulatory RNAs as examples, we will investigate bacterial adaptation in the kidney at the gene regulatory and functional levels. We will analyze global bacterial and host gene expression in the infected kidney using dual RNA-seq in a murine infection model. Furthermore, we will use reporter gene modules, tissue clearing, and lightsheet microscopy as well as two-photon microscopy to follow the expression of these factors in the infected organ or during the course of infection. Further functional characterization will include in vitro studies of the interaction between UPEC isolates or defined mutants and isolated collecting ducts under different growth and infection conditions.