title: A metaproteomics approach to elucidate host and pathogen protein expression during catheter-associated urinary tract infections (CAUTIs).
abstract: Long-term catheterization inevitably leads to a catheter-associated bacteriuria caused by multispecies bacterial biofilms growing on and in the catheters. The overall goal of the presented study was (1) to unravel bacterial community structure and function of such a uropathogenic biofilm and (2) to elucidate the interplay between bacterial virulence and the human immune system within the urine. To this end, a metaproteomics approach combined with in vitro proteomics analyses was employed to investigate both, the pro- and eukaryotic protein inventory. Our proteome analyses demonstrated that the biofilm of the investigated catheter is dominated by three bacterial species, that is, Pseudomonas aeruginosa, Morganella morganii, and Bacteroides sp., and identified iron limitation as one of the major challenges in the bladder environment. In vitro proteome analysis of P. aeruginosa and M. morganii isolated from the biofilm revealed that these opportunistic pathogens are able to overcome iron restriction via the production of siderophores and high expression of corresponding receptors. Notably, a comparison of in vivo and in vitro protein profiles of P. aeruginosa and M. morganii also indicated that the bacteria employ different strategies to adapt to the urinary tract. Although P. aeruginosa seems to express secreted and surface-exposed proteases to escape the human innate immune system and metabolizes amino acids, M. morganii is able to take up sugars and to degrade urea. Most interestingly, a comparison of urine protein profiles of three long-term catheterized patients and three healthy control persons demonstrated the elevated level of proteins associated with neutrophils, macrophages, and the complement system in the patient's urine, which might point to a specific activation of the innate immune system in response to biofilm-associated urinary tract infections. We thus hypothesize that the often asymptomatic nature of catheter-associated urinary tract infections might be based on a fine-tuned balance between the expression of bacterial virulence factors and the human immune system.
authors: From the ‡Institute of Microbiology, University of Greifswald, 17489 Greifswald, Friedrich-Ludwig-Jahn-Strasse 15, Germany; §Institute of Microbiology, Technische Universität Braunschweig, 38106 Braunschweig, Spielmannstrasse 7, Germany;
authors: Christian
authors: C
authors: Lassek
authors: §Institute of Microbiology, Technische Universität Braunschweig, 38106 Braunschweig, Spielmannstrasse 7, Germany;
authors: Melanie
authors: M
authors: Burghartz
authors: ¶Microbial Interactions and Processes Research Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Inhoffenstrasse 7, Germany;
authors: Diego
authors: D
authors: Chaves-Moreno
authors: From the ‡Institute of Microbiology, University of Greifswald, 17489 Greifswald, Friedrich-Ludwig-Jahn-Strasse 15, Germany;
authors: Andreas
authors: A
authors: Otto
authors: From the ‡Institute of Microbiology, University of Greifswald, 17489 Greifswald, Friedrich-Ludwig-Jahn-Strasse 15, Germany;
authors: Christian
authors: C
authors: Hentschker
authors: From the ‡Institute of Microbiology, University of Greifswald, 17489 Greifswald, Friedrich-Ludwig-Jahn-Strasse 15, Germany;
authors: Stephan
authors: S
authors: Fuchs
authors: From the ‡Institute of Microbiology, University of Greifswald, 17489 Greifswald, Friedrich-Ludwig-Jahn-Strasse 15, Germany;
authors: Jörg
authors: J
authors: Bernhardt
authors: ¶Microbial Interactions and Processes Research Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Inhoffenstrasse 7, Germany;
authors: Ruy
authors: R
authors: Jauregui
authors: ‖Urologist's Practice, Kassel, Germany.
authors: Rüdiger
authors: R
authors: Neubauer
authors: From the ‡Institute of Microbiology, University of Greifswald, 17489 Greifswald, Friedrich-Ludwig-Jahn-Strasse 15, Germany;
authors: Dörte
authors: D
authors: Becher
authors: ¶Microbial Interactions and Processes Research Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Inhoffenstrasse 7, Germany;
authors: Dietmar H
authors: DH
authors: Pieper
authors: §Institute of Microbiology, Technische Universität Braunschweig, 38106 Braunschweig, Spielmannstrasse 7, Germany;
authors: Martina
authors: M
authors: Jahn
authors: §Institute of Microbiology, Technische Universität Braunschweig, 38106 Braunschweig, Spielmannstrasse 7, Germany;
authors: Dieter
authors: D
authors: Jahn
authors: From the ‡Institute of Microbiology, University of Greifswald, 17489 Greifswald, Friedrich-Ludwig-Jahn-Strasse 15, Germany; ¶Microbial Interactions and Processes Research Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Inhoffenstrasse 7, Germany; riedela@uni-greifswald.de.
authors: Katharina
authors: K
authors: Riedel
mesh_terms: D000222:Adaptation, Physiological; D001426:Bacterial Proteins / Q000378:metabolism*; D018441:Biofilms; D055499:Catheter-Related Infections / Q000378:metabolism* / Q000382:microbiology* / Q000652:urine; D002474:Cell-Free System; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D020613:Morganella morganii / Q000302:isolation & purification / Q000378:metabolism; D010641:Phenotype; D040901:Proteomics / Q000379:methods*; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification / Q000378:metabolism; D013045:Species Specificity; D014551:Urinary Tract / Q000382:microbiology / Q000473:pathology; D014552:Urinary Tract Infections / Q000378:metabolism* / Q000382:microbiology* / Q000652:urine; D014556:Urine / Q000382:microbiology
chemical_list: D001426:Bacterial Proteins