The lac operon in uropathogenic Escherichia coli enhances intracellular growth by enabling host glycan utilization.

The lac operon in Escherichia coli has been used as a model of gene regulation throughout biology since its characterization in the early 1960s. Despite the myriad of biotechnology applications that arose from characterization of the lac system, the explanation for the importance of a functional lac operon in normal bladder colonization by uropathogenic E. coli remains unknown given that the prototypical substrate, lactose, is not normally known to be readily available within the urinary tract. Here, we identified a unique uropathogenic clinical isolate (5.3r) that has a two codon deletion in the LacY permease, leading to impaired β-galactoside metabolism and attenuation of development of critical intracellular bacterial communities (IBCs) in which UPEC replicates to high numbers, and then disseminates during urinary tract infection. Further, we show that expression of a functional lacY permease gene is sufficient to rescue defects in IBC size and number in 5.3r. In addition, we demonstrate that UPEC are able to utilize the disaccharide galactose β-1,4 N-acetylglucosamine (LacNAc) - which appears as the terminal glycan in a subset of the glycoproteins that decorate the apical surface of bladder epithelial cells - as a sole carbon source in a lac system dependent manner. These data suggest that the lac operon is important to the growth and development of intracellular E. coli through metabolism of host bladder cell glycans.