Purine Biosynthesis Metabolically Constrains Intracellular Survival of Uropathogenic Escherichia coli.

Shaffer CL, Zhang EW, Dudley AG, Dixon BREA, Guckes KR, Breland EJ, Floyd KA, Casella DP, Algood HMS, Clayton DB, Hadjifrangiskou M
Infect Immun. 2017 85 (1)

PMID: 27795353 · PMCID: PMC5203662 · DOI:10.1128/IAI.00471-16

The ability to de novo synthesize purines has been associated with the intracellular survival of multiple bacterial pathogens. Uropathogenic Escherichia coli (UPEC), the predominant cause of urinary tract infections, undergoes a transient intracellular lifestyle during which bacteria clonally expand into multicellular bacterial communities within the cytoplasm of bladder epithelial cells. Here, we characterized the contribution of the conserved de novo purine biosynthesis-associated locus cvpA-purF to UPEC pathogenesis. Deletion of cvpA-purF, or of purF alone, abolished de novo purine biosynthesis but did not impact bacterial adherence properties in vitro or in the bladder lumen. However, upon internalization by bladder epithelial cells, UPEC deficient in de novo purine biosynthesis was unable to expand into intracytoplasmic bacterial communities over time, unless it was extrachromosomally complemented. These findings indicate that UPEC is deprived of purine nucleotides within the intracellular niche and relies on de novo purine synthesis to meet this metabolic requirement.

Copyright © 2016 American Society for Microbiology.

MeSH Terms (14)

Animals Cytoplasm Epithelial Cells Escherichia coli Infections Escherichia coli Proteins Female Humans Mice Mice, Inbred C3H Purines Urinary Bladder Urinary Tract Infections Uropathogenic Escherichia coli Virulence

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