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Purine Biosynthesis Metabolically Constrains Intracellular Survival of Uropathogenic Escherichia coli

Shaffer, Carrie L. and Zhang, Ellisa W. and Dudley, Anne G. and Dixon, Beverly R. E. A. and Guckes, Kirsten R. and Breland, Erin J. and Floyd, Kyle A. and Casella, Daniel P. and Algood, Holly M. Scott and Clayton, Douglass B. and Hadjifrangiskou, Maria (2017) Purine Biosynthesis Metabolically Constrains Intracellular Survival of Uropathogenic Escherichia coli. Infection and Immunity, 85 (1). Art. No. e00471-16. ISSN 0019-9567. PMCID PMC5203662. http://resolver.caltech.edu/CaltechAUTHORS:20170331-075358953

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1128/IAI.00471-16DOIArticle
http://iai.asm.org/content/85/1/e00471-16PublisherArticle
http://iai.asm.org/content/85/1/e00471-16/suppl/DCSupplementalPublisherSupplemental Material
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5203662/PubMed CentralArticle
ORCID:
AuthorORCID
Algood, Holly M. Scott0000-0003-3735-4649
Additional Information:© 2016 American Society for Microbiology. Received 3 June 2016. Returned for modification 9 July 2016. Accepted 10 October 2016. Accepted manuscript posted online 17 October 2016. 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. FUNDING INFORMATION Department of Veterans Affairs IBX000915A Holly M. Scott Algood HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) https://doi.org/10.13039/100000062F32DK105720 Carrie Shaffer HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) https://doi.org/10.13039/1000000626K08DK106472-02 Douglass B. Clayton Vanderbilt University https://doi.org/10.13039/1000065371-040520-9211 Maria Hadjifrangiskou National Kidney Foundation (NKF) https://doi.org/10.13039/100001259Young Investigator Award Maria Hadjifrangiskou
Funders:
Funding AgencyGrant Number
Department of Veterans AffairsIBX000915A
NIHF32DK105720
NIH6K08DK106472-02
Vanderbilt University1-040520-9211
National Kidney FoundationUNSPECIFIED
Subject Keywords:E. coli, UPEC, bladder, intracellular, urinary tract infection
PubMed Central ID:PMC5203662
Record Number:CaltechAUTHORS:20170331-075358953
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20170331-075358953
Official Citation:Shaffer CL, Zhang EW, Dudley AG, Dixon BREA, Guckes KR, Breland EJ, Floyd KA, Casella DP, Algood HMS, Clayton DB, Hadjifrangiskou M. 2017. Purine biosynthesis metabolically constrains intracellular survival of uropathogenic Escherichia coli. Infect Immun 85:e00471-16. https://doi.org/10.1128/IAI.00471-16.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75565
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:31 Mar 2017 15:16
Last Modified:10 May 2017 22:41

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