title: Ribonuclease 7, an antimicrobial peptide upregulated during infection, contributes to microbial defense of the human urinary tract.
abstract: The mechanisms that maintain sterility in the urinary tract are incompletely understood; however, recent studies stress the importance of antimicrobial peptides in protecting the urinary tract from infection. Ribonuclease 7 (RNase 7), a potent antimicrobial peptide contributing to urinary tract sterility, is expressed by intercalated cells in the renal collecting tubules and is present in the urine at levels sufficient to kill bacteria at baseline. Here, we characterize the expression and function of RNase 7 in the human urinary tract during infection. Both quantitative real-time PCR and enzyme-linked immunosorbant assays demonstrated increases in RNASE7 expression in the kidney along with kidney and urinary RNase 7 peptide concentrations with infection. While immunostaining localized RNase 7 production to the intercalated cells of the collecting tubule during sterility, its expression during pyelonephritis was found to increase throughout the nephron but not in glomeruli or the interstitium. Recombinant RNase 7 exhibited antimicrobial activity against uropathogens at low micromolar concentrations by disrupting the microbial membrane as determined by atomic force microscopy. Thus, RNase 7 expression is increased in the urinary tract with infection and has antibacterial activity against uropathogens at micromolar concentrations.
authors.affiliation: Department of Pediatrics, Division of Nephrology, Nationwide Children's Hospital, Columbus, Ohio 43205, USA.
authors.forename: John David
authors.initials: JD
authors.lastname: Spencer
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Schwaderer
authors.forename: Huanyu
authors.initials: H
authors.lastname: Wang
authors.forename: Julianne
authors.initials: J
authors.lastname: Bartz
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kline
authors.forename: Tad
authors.initials: T
authors.lastname: Eichler
authors.forename: Kristin R
authors.initials: KR
authors.lastname: DeSouza
authors.forename: Sunder
authors.initials: S
authors.lastname: Sims-Lucas
authors.forename: Peter
authors.initials: P
authors.lastname: Baker
authors.forename: David S
authors.initials: DS
authors.lastname: Hains
mesh_terms: D001419:Bacteria / Q000201:enzymology; D016022:Case-Control Studies; D002462:Cell Membrane / Q000201:enzymology; D004797:Enzyme-Linked Immunosorbent Assay; D054884:Host-Pathogen Interactions; D006801:Humans; D007668:Kidney / Q000201:enzymology* / Q000382:microbiology; D007700:Kinetics; D050296:Microbial Viability; D018625:Microscopy, Atomic Force; D011704:Pyelonephritis / Q000201:enzymology* / Q000235:genetics / Q000382:microbiology / Q000652:urine; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D015854:Up-Regulation; D014552:Urinary Tract Infections / Q000201:enzymology* / Q000235:genetics / Q000382:microbiology / Q000652:urine
chemical_list: D012333:RNA, Messenger; D012260:Ribonucleases; C470000:Ribonuclease 7