Amino Sugar Metabolism with AgaSY Coordinates Carbon Catabolism, Fimbrial Regulation, and Pathogenesis in Uropathogenic E. coli
Year: 2026
Type: preprint
Abstract: Uropathogenic Escherichia coli (UPEC) exploit alternative carbon sources in order to adapt to the nutrient-limited urinary tract. While glucose is often scarce in healthy human urine, UPEC express a variety of sugar transport and catabolic systems that promote fitness during infection. In this study, we identify the agaSY genes in UPEC strain CFT073 as essential for the catabolism of the amino sugars N-acetyl-galactosamine (GalNAc or Aga) and galactosamine (GalN or Gam) and for the efficient use of additional amino sugars and carbon sources. Deletion of agaSY not only abolished Aga utilization but also impaired catabolism of multiple carbon sources, including amino acids and sugars tested using phenotypic arrays. The Δ agaSY mutant exhibited significantly reduced type 1 fimbriae production, reduced biofilm formation, and increased motility, suggesting a link between amino sugar metabolism and the regulation of bacterial surface structures. Loss of agaSY did not affect growth and adherence to bladder cells and increased expression of genes encoding F9 fimbriae. Furthermore, the Δ agaSY mutant was significantly attenuated for bladder and kidney colonization in a murine urinary tract infection model, while complementation restored urinary tract colonization. The results indicate that a combination of deficiencies in nutrient acquisition, altered carbon metabolism, and regulation of virulence-associated factors contributes to reduced urinary tract colonization. Our findings highlight the interplay between metabolic flexibility and virulence regulation, as well as the central role that amino sugar metabolism plays in UPEC pathogenesis. Author Summary Urinary tract infections are among the most common bacterial infections, and most are caused by uropathogenic Escherichia coli. To survive and cause infection, these bacteria need to take up nutrients from the urinary tract, where the available nutrients can be limited. In this study, we were interested in the impact of the ability of E. coli to utilize different nutrients and to use them to cause urinary tract infections. We focused on two genes that allow E. coli to metabolize amino sugars, a group of nutrients that can be found in the urinary tract. We found that these genes are important not just for using these sugars but also for using many other nutrients. Knocking out these genes affected several mechanisms such as surface structure production, motility and biofilm formation. Most importantly, bacteria lacking these genes were less able to colonize the bladder and kidneys in mice, and restoring the genes restored this ability. We demonstrate a close link between nutrient use and the regulation of virulence factors, particularly fimbrial genes. Understanding this link may help to clarify how E. coli can adapt to the urinary tract and identify new ways to interfere with bacterial infection.
Language: English
Subfield: Microbiology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Award: G2583879797
OpenAlex ID: W7222931873