title: VISLISI trial, a prospective clinical study allowing identification of a new metalloprotease and putative virulence factor from Staphylococcus lugdunensis.
abstract: OBJECTIVE
  Staphylococcus lugdunensis is a coagulase-negative staphylococcus that displays an unusually high virulence rate close to that of Staphylococcus aureus. It also shares phenotypic properties with S. aureus and several studies found putative virulence factors. The objective of the study was to describe the clinical manifestations of S. lugdunensis infections and investigate putative virulence factors.
  
  
  METHODS
  We conducted a prospective study from November 2013 to March 2016 at the University Hospital of Strasbourg. Putative virulence factors were investigated by clumping factor detection, screening for proteolytic activity, and sequence analysis using tandem nano-liquid chromatography-mass spectrometry.
  
  
  RESULTS
  In total, 347 positive samples for S. lugdunensis were collected, of which 129 (37.2%) were from confirmed cases of S. lugdunensis infection. Eighty-one of these 129 patients were included in the study. Bone and prosthetic joints (PJI) were the most frequent sites of infection (n=28; 34.6%) followed by skin and soft tissues (n=23; 28.4%). We identified and purified a novel protease secreted by 50 samples (61.7%), most frequently associated with samples from deep infections and PJI (pr 0.97 and pr 0.91, respectively). Protease peptide sequencing by nano-liquid chromatography-mass spectrometry revealed a novel protease bearing 62.42% identity with ShpI, a metalloprotease secreted by Staphylococcus hyicus.
  
  
  CONCLUSIONS
  This study confirms the pathogenicity of S. lugdunensis, particularly in bone and PJI. We also identified a novel metalloprotease called lugdulysin that may contribute to virulence.
authors.affiliation: Hôpitaux Universitaires, Maladies Infectieuses et Tropicales, Strasbourg, France; Université de Strasbourg, CHRU de Strasbourg, VBP EA7290, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Institut de Bactériologie, 3 Rue Koeberlé, Strasbourg, France. Electronic address: xavier.argemi@chru-strasbourg.fr.
authors.forename: X
authors.initials: X
authors.lastname: Argemi
authors.affiliation: Université de Strasbourg, CHRU de Strasbourg, VBP EA7290, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Institut de Bactériologie, 3 Rue Koeberlé, Strasbourg, France; Hôpitaux Universitaires, Laboratoire de Microbiologie, Strasbourg, France.
authors.forename: G
authors.initials: G
authors.lastname: Prévost
authors.affiliation: Université de Strasbourg, CHRU de Strasbourg, VBP EA7290, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Institut de Bactériologie, 3 Rue Koeberlé, Strasbourg, France; Hôpitaux Universitaires, Laboratoire de Microbiologie, Strasbourg, France.
authors.forename: P
authors.initials: P
authors.lastname: Riegel
authors.affiliation: Hôpitaux Universitaires, Laboratoire de Microbiologie, Strasbourg, France.
authors.forename: D
authors.initials: D
authors.lastname: Keller
authors.affiliation: Hôpitaux Universitaires, Service de Santé Publique, Strasbourg, France.
authors.forename: N
authors.initials: N
authors.lastname: Meyer
authors.affiliation: Hôpitaux Universitaires, Maladies Infectieuses et Tropicales, Strasbourg, France.
authors.forename: M
authors.initials: M
authors.lastname: Baldeyrou
authors.affiliation: Hôpitaux Universitaires, Maladies Infectieuses et Tropicales, Strasbourg, France.
authors.forename: N
authors.initials: N
authors.lastname: Douiri
authors.affiliation: Hôpitaux Universitaires, Maladies Infectieuses et Tropicales, Strasbourg, France.
authors.forename: N
authors.initials: N
authors.lastname: Lefebvre
authors.affiliation: Hôpitaux Universitaires, Immunologie Clinique, Strasbourg, France.
authors.forename: K
authors.initials: K
authors.lastname: Meghit
authors.affiliation: Hôpitaux Universitaires, Service de Chirurgie Orthopédique, CCOM, Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Ronde Oustau
authors.affiliation: Hôpitaux Universitaires, Maladies Infectieuses et Tropicales, Strasbourg, France; Université de Strasbourg, CHRU de Strasbourg, VBP EA7290, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Institut de Bactériologie, 3 Rue Koeberlé, Strasbourg, France.
authors.forename: D
authors.initials: D
authors.lastname: Christmann
authors.affiliation: Laboratoire de Spectrométrie de Masse Bio-Organique, Département des Sciences Analytiques, Institut Pluridisciplinaire Hubert Curien, UMR 7178 (CNRS-UdS), Strasbourg, France.
authors.forename: S
authors.initials: S
authors.lastname: Cianférani
authors.affiliation: Laboratoire de Spectrométrie de Masse Bio-Organique, Département des Sciences Analytiques, Institut Pluridisciplinaire Hubert Curien, UMR 7178 (CNRS-UdS), Strasbourg, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Strub
authors.affiliation: Hôpitaux Universitaires, Maladies Infectieuses et Tropicales, Strasbourg, France; Université de Strasbourg, CHRU de Strasbourg, VBP EA7290, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Institut de Bactériologie, 3 Rue Koeberlé, Strasbourg, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Hansmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000617:Aminoglycosides / Q000627:therapeutic use; D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D004917:Erythromycin / Q000627:therapeutic use; D005260:Female; D024841:Fluoroquinolones / Q000627:therapeutic use; D005500:Follow-Up Studies; D005578:Fosfomycin / Q000627:therapeutic use; D005672:Fusidic Acid / Q000627:therapeutic use; D006801:Humans; D008297:Male; D045726:Metalloproteases / Q000235:genetics* / Q000378:metabolism; D008712:Methicillin / Q000627:therapeutic use; D008875:Middle Aged; D010746:Phosphonoacetic Acid / Q000627:therapeutic use; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000175:diagnosis / Q000188:drug therapy; D057787:Staphylococcus lugdunensis / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D014640:Vancomycin / Q000627:therapeutic use; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D000617:Aminoglycosides; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D037521:Virulence Factors; D005578:Fosfomycin; D005672:Fusidic Acid; D004917:Erythromycin; D014640:Vancomycin; D045726:Metalloproteases; D010746:Phosphonoacetic Acid; D008712:Methicillin
keywords: Bone and joint infections; Mass spectrometry; Metalloprotease; Staphylococcus lugdunensis; Virulence factors