title: Diagnosing inflammation and infection in the urinary system via proteomics.
abstract: BACKGROUND
  Current methodology for the diagnosis of diseases in the urinary system includes patient symptomology, urine analysis and urine culture. Asymptomatic bacteriuria from urethral colonization or indwelling catheters, sample contamination from perineal or vaginal sources, and non-infectious inflammatory conditions can mimic UTIs, leading to uncertainty on medical treatment decisions.
  
  
  METHODS
  Innovative shotgun metaproteomic methods were used to analyze urine sediments from 120 patients also subjected to conventional urinalysis for various clinical reasons including suspected UTIs. The proteomic data were simultaneously searched for the presence of microbial agents, inflammation, immune responses against pathogens, and evidence of urothelial tissue injury. Hierarchical clustering analysis was performed to identify host protein patterns discerning UTI from urethral colonization and vaginal contamination of urine samples.
  
  
  RESULTS
  Organisms causing more than 98% of all UTIs and commensal microbes of the urogenital and perineal area were identified from 76 urine sediments with detection sensitivities estimated to be similar to urine culture. Proteomic data permitted a thorough evaluation of inflammatory and antimicrobial immune responses. Hierarchical clustering of the data revealed that high abundances of proteins from activated neutrophils were associated with pathogens in most cases, and correlated well with leukocyte esterase activities and leukocyte counts via microscopy. Proteomic data also allowed assessments of urothelial injury, by quantifying proteins highly expressed in red blood cells and contributing to the acute phase response. Lactobacillus and Gardnerella vaginalis were frequently identified suggesting urethral colonization and/or vaginal contamination of urine.
  
  
  CONCLUSIONS
  A metaproteomic approach of interest for routine urine clinical diagnostics is presented. As compared to urinalysis and urine culture methods, the data are derived from a single experiment for a given sample and provide additional insights into presence or absence of inflammatory responses and vaginal contamination of urine specimens.
authors.affiliation: The J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD, 20850, USA. yayu@jcvi.org.
authors.forename: Yanbao
authors.initials: Y
authors.lastname: Yu
authors.affiliation: The J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD, 20850, USA. patrycjasikorski@gmail.com.|Current affiliation: Department of Microbiology and Immunology, Georgetown University, 37th and O Streets, NW, Washington, D.C., 20057, USA. patrycjasikorski@gmail.com.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sikorski
authors.affiliation: Quest Diagnostics at Shady Grove Adventist Hospital, 9901 Medical Center Drive, Rockville, MD, 20850, USA. Cynthia.X.Bowmangholston@questdiagnostics.com.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Bowman-Gholston
authors.affiliation: Advanced Pathology Associates LLC at Shady Grove Adventist Hospital, 9901 Medical Center Drive, Rockville, MD, 20850, USA. Ncacciab@adventisthealthcare.com.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cacciabeve
authors.affiliation: The J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD, 20850, USA. kenelson@jcvi.org.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Nelson
authors.affiliation: The J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD, 20850, USA. rpieper@jcvi.org.
authors.forename: Rembert
authors.initials: R
authors.lastname: Pieper
mesh_terms: D001419:Bacteria / Q000302:isolation & purification; D002853:Chromatography, Liquid; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000378:metabolism; D040901:Proteomics; D053719:Tandem Mass Spectrometry; D014521:Urethra / Q000382:microbiology; D014552:Urinary Tract Infections / Q000175:diagnosis* / Q000378:metabolism