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.
|Journal||Infection and Immunity|
|State||Published - 2017|
Bibliographical noteFunding Information:
We thank Timothy Cover for the use of specialized equipment. The authors declare no competing interests. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. C.L.S. and M.H. conceptualized and designed the experiments. C.L.S., E.W.Z., A.G.D., D.P.C., B.R.E.A.D., and K.A.F. performed experiments. E.J.B. and K.R.G. provided technical support. D.B.C. and H.M.S.A. contributed essential reagents and isolated PMNs. C.L.S., D.B.C., H.M.S.A., and M.H. analyzed data. C.L.S. and M.H. wrote the manuscript.
© 2016 American Society for Microbiology. All Rights Reserved.
- E. coli
- Urinary tract infection
ASJC Scopus subject areas
- Infectious Diseases