Purine biosynthesis metabolically constrains intracellular survival of uropathogenic Escherichia coli

Carrie L. Shaffer, Ellisa W. Zhang, Anne G. Dudley, Beverly R.E.A. Dixon, Kirsten R. Guckes, Erin J. Breland, Kyle A. Floyd, Daniel P. Casella, Holly M.Scott Algood, Douglass B. Clayton, Maria Hadjifrangiskou

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere00471-16
JournalInfection and Immunity
Volume85
Issue number1
DOIs
StatePublished - 2017

Bibliographical note

Publisher Copyright:
© 2016 American Society for Microbiology. All Rights Reserved.

Keywords

  • Bladder
  • E. coli
  • Intracellular
  • UPEC
  • Urinary tract infection

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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