Title

Purine biosynthesis metabolically constrains intracellular survival of uropathogenic Escherichia coli

Document Type

Journal Article

Publication Date

1-1-2017

Journal

Infection and Immunity

Volume

85

Issue

1

DOI

10.1128/IAI.00471-16

Keywords

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

Abstract

© 2016 American Society for Microbiology. All Rights Reserved. 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.

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