Amino Sugar Metabolism with AgaSY Coordinates Carbon Catabolism, Fimbrial Regulation, and Pathogenesis in Uropathogenic E. coli

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 {Delta}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 {Delta}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.