title: Purine Biosynthesis Metabolically Constrains Intracellular Survival of Uropathogenic Escherichia coli.
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.
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: Carrie L
authors: CL
authors: Shaffer
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: Ellisa W
authors: EW
authors: Zhang
authors: Division of Pediatric Urology, Vanderbilt University Medical Center, and Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee, USA.
authors: Anne G
authors: AG
authors: Dudley
authors: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
authors: Beverly R E A
authors: BREA
authors: Dixon
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: Kirsten R
authors: KR
authors: Guckes
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: Erin J
authors: EJ
authors: Breland
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: Kyle A
authors: KA
authors: Floyd
authors: Division of Pediatric Urology, Vanderbilt University Medical Center, and Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee, USA.
authors: Daniel P
authors: DP
authors: Casella
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
authors: Holly M Scott
authors: HMS
authors: Algood
authors: Division of Pediatric Urology, Vanderbilt University Medical Center, and Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee, USA.
authors: Douglass B
authors: DB
authors: Clayton
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA maria.hadjifrangiskou@vanderbilt.edu.|Division of Pediatric Urology, Vanderbilt University Medical Center, and Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee, USA.
authors: Maria
authors: M
authors: Hadjifrangiskou
mesh_terms: D000818:Animals; D003593:Cytoplasm / Q000378:metabolism / Q000382:microbiology; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D004927:Escherichia coli Infections / Q000378:metabolism / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D011687:Purines / Q000096:biosynthesis* / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism / Q000382:microbiology; D014552:Urinary Tract Infections / Q000378:metabolism / Q000382:microbiology; D056689:Uropathogenic Escherichia coli / Q000378:metabolism*; D014774:Virulence / Q000235:genetics
chemical_list: D029968:Escherichia coli Proteins; D011687:Purines; C030985:purine
keywords: E. coli; UPEC; bladder; intracellular; urinary tract infection