SUMMARYUropathogenic Escherichia coli (UPEC) strains cause a majority of urinary tract infections (UTIs). Since UPEC strains can become antibiotic resistant, adjunct or alternate therapies are urgently needed. UPEC strains grow extremely rapidly in patients with UTIs. Thus, this review focuses on the relation between urine composition and UPEC growth and metabolism. Compilation of urinary components from two major data sources suggests the presence of sufficient amino acids and carbohydrates as energy sources and abundant phosphorus, sulfur, and nitrogen sources. In a mouse UTI model, mutants lacking enzymes of the tricarboxylic acid cycle, gluconeogenesis, and the nonoxidative branch of the pentose cycle are less competitive than the corresponding parental strains, which is consistent with amino acids as major energy sources. Other evidence suggests that carbohydrates are required energy sources. UPEC strains in urine ex vivo and in vivo express transporters for peptides, amino acids, carbohydrates, and iron and genes associated with nitrogen limitation, amino acid synthesis, nucleotide synthesis, and nucleotide salvage. Mouse models confirm the requirement for many, but not all, of these genes. Laboratory evolution studies suggest that rapid nutrient uptake without metabolic rewiring is sufficient to account for rapid growth. Proteins and pathways required for rapid growth should be considered potential targets for alternate or adjunct therapies.
Clinical microbiology reviews. 2019 Oct 16*** epublish ***
Larry Reitzer, Philippe Zimmern
Department of Biological Sciences, University of Texas at Dallas, Richardson, Texas, USA ., Department of Urology, University of Texas Southwestern Medical School, Dallas, Texas, USA.