title: The N-terminal domain of the thermo-regulated surface protein PrpA of Enterococcus faecium binds to fibrinogen, fibronectin and platelets.
abstract: Enterococcus faecium is a commensal of the mammalian gastrointestinal tract, but is also found in non-enteric environments where it can grow between 10 °C and 45 °C. E. faecium has recently emerged as a multi-drug resistant nosocomial pathogen. We hypothesized that genes involved in the colonization and infection of mammals exhibit temperature-regulated expression control and we therefore performed a transcriptome analysis of the clinical isolate E. faecium E1162, during mid-exponential growth at 25 °C and 37 °C. One of the genes that exhibited differential expression between 25 °C and 37 °C, was predicted to encode a peptidoglycan-anchored surface protein. The N-terminal domain of this protein is unique to E. faecium and closely related enterococci, while the C-terminal domain is homologous to the Streptococcus agalactiae surface protein BibA. This region of the protein contains proline-rich repeats, leading us to name the protein PrpA for proline-rich protein A. We found that PrpA is a surface-exposed protein which is most abundant during exponential growth at 37 °C in E. faecium E1162. The heterologously expressed and purified N-terminal domain of PrpA was able to bind to the extracellular matrix proteins fibrinogen and fibronectin. In addition, the N-terminal domain of PrpA interacted with both non-activated and activated platelets.
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Guzmán Prieto
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Rolf T
authors.initials: RT
authors.lastname: Urbanus
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Xinglin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Damien
authors.initials: D
authors.lastname: Bierschenk
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: C Arnold
authors.initials: CA
authors.lastname: Koekman
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Miranda
authors.initials: M
authors.lastname: van Luit-Asbroek
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Janneke P
authors.initials: JP
authors.lastname: Ouwerkerk
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Pape
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Fernanda L
authors.initials: FL
authors.lastname: Paganelli
authors.affiliation: Division of Infectious Diseases, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Dominique
authors.initials: D
authors.lastname: Wobser
authors.affiliation: Division of Infectious Diseases, University Medical Center Freiburg, Freiburg, Germany.|Division of Pediatric Infectious Diseases, Hauner Children´s Hospital, Ludwigs Maximilian University Munich, Munich, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Huebner
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Antoni P A
authors.initials: AP
authors.lastname: Hendrickx
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marc J M
authors.initials: MJ
authors.lastname: Bonten
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Rob J L
authors.initials: RJ
authors.lastname: Willems
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Willem
authors.initials: W
authors.lastname: van Schaik
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001792:Blood Platelets / Q000378:metabolism*; D003428:Cross Infection / Q000382:microbiology; D016984:Enterococcus faecium / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D005340:Fibrinogen / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D010457:Peptidoglycan / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D013696:Temperature
chemical_list: D001426:Bacterial Proteins; D005353:Fibronectins; D008565:Membrane Proteins; D010457:Peptidoglycan; D005340:Fibrinogen