Metabolic Adaptations of Uropathogenic E. coli in the Urinary Tract

Abstract

Escherichia coli ordinarily resides in the lower gastrointestinal tract in humans, but some strains, known as Uropathogenic E. coli (UPEC), are also adapted to the relatively harsh environment of the urinary tract. Infections of the urine, bladder and kidneys by UPEC may lead to potentially fatal bloodstream infections. To survive this range of conditions, UPEC strains must have broad and flexible metabolic capabilities and efficiently utilize scarce essential nutrients. Whole-organism (or "omics") methods have recently provided significant advances in our understanding of the importance of metabolic adaptation in the success of UPECs. Here we describe the nutritional and metabolic requirements for UPEC infection in these environments, and focus on particular metabolic responses and adaptations of UPEC that appear to be essential for survival in the urinary tract.

Keywords: UPEC; metabolism; metabolomics; urinary tract infections; uropathogenic E. coli; virulence.

Figure 1

UPEC pathogenesis across multiple microenvironments: Uropathogenic E. coli harmlessly grow in the human intestines as part of the microbiome. Within this environment, UPEC interact with the intestinal epithelial cells in a symbiotic relationship, however there is competition for nutrients between other microorganisms. UPEC has also adapted the ability to cause urinary tract infections and urosepsis by transitioning to a pathogenic lifecycle in the urinary tract and bloodstream. To gain a stronghold within the urinary tract, UPEC express numerous pili systems to facilitate attachment to the superficial bladder epithelial cell layer. Invasion into the host cell initiates replication immediately to form IBCs and a subpopulation undergoes cell elongation (filamentation). Eventually the epithelial cell is overloaded and UPEC escape, rupturing open the host cell releasing motile short and elongated cells which can infect neighboring host epithelia to continue the infective cycle.

Figure 2

Summarized view of the main metabolic responses of UPEC during urinary tract infection, as detailed in text under the section “Genetic and metabolic responses in UPEC pathogenesis.” In comparison to the intestine, wherein glycolysis and Entner-Doudoroff pathways are shown to be important for UPEC survival, UPEC in the urinary tract displays a number of metabolic adaptations in central carbon metabolism, amino catabolism and other pathways, to cause infection in the urinary tract. Genes identified to play a role in UPEC pathogenesis are shown, having detailed information in text. Genes in blue color denote genes that play a role in UPEC fitness in the urinary tract, or result in attenuation in a mouse or in vitro model of invasion and intracellular bacterial community formation. The gene in red denotes a gene specifically identified to play a role in kidney infection. Transporters are shown in green boxes over the cell membrane. sdhB, succinate dehydrogenase; pckA, phosphoenolpyruvate carboxykinase; tpiA, triosephosphate isomerase; srlA, sorbitol transporter; lacZ, β-galactosidase; galK, galactokinase; dsdX, D-serine specific transporter; dsdA, D-serine deaminase; dppA, periplasmic dipeptide transport protein; oppA, periplasmic oligopeptide-binding protein; tonB, ferric iron uptake mediator; pur, genes involved in purine synthesis.

Figure 3

Metabolism as a potential target for the development of new drugs and vaccines for UTIs, and the use of urine as a diagnostic fluid for UTI detection; each with potential pros and cons associated with them. These potential targets are suggested by the authors as per the literature search.