title: Staphylococcus aureus infective endocarditis versus bacteremia strains: Subtle genetic differences at stake.
abstract: Infective endocarditis (IE)((1)) is a severe condition complicating 10-25% of Staphylococcus aureus bacteremia. Although host-related IE risk factors have been identified, the involvement of bacterial features in IE complication is still unclear. We characterized strictly defined IE and bacteremia isolates and searched for discriminant features. S. aureus isolates causing community-acquired, definite native-valve IE (n=72) and bacteremia (n=54) were collected prospectively as part of a French multicenter cohort. Phenotypic traits previously reported or hypothesized to be involved in staphylococcal IE pathogenesis were tested. In parallel, the genotypic profiles of all isolates, obtained by microarray, were analyzed by discriminant analysis of principal components (DAPC)((2)). No significant difference was observed between IE and bacteremia strains, regarding either phenotypic or genotypic univariate analyses. However, the multivariate statistical tool DAPC, applied on microarray data, segregated IE and bacteremia isolates: IE isolates were correctly reassigned as such in 80.6% of the cases (C-statistic 0.83, P<0.001). The performance of this model was confirmed with an independent French collection IE and bacteremia isolates (78.8% reassignment, C-statistic 0.65, P<0.01). Finally, a simple linear discriminant function based on a subset of 8 genetic markers retained valuable performance both in study collection (86.1%, P<0.001) and in the independent validation collection (81.8%, P<0.01). We here show that community-acquired IE and bacteremia S. aureus isolates are genetically distinct based on subtle combinations of genetic markers. This finding provides the proof of concept that bacterial characteristics may contribute to the occurrence of IE in patients with S. aureus bacteremia.
authors: Laboratoire de Bactériologie, Centre de Biologie Est, Hospices Civils de Lyon, 59 Boulevard Louis Pinel, 69677 Bron Cedex, France; CIRI, International Center for Infectiology Research, Inserm U1111, Université Lyon 1, Ecole Normale Supérieure de Lyon, CNRS UMR5308, 7 rue Guillaume Paradin, 69008 Lyon, France; Centre National de Référence des Staphylocoques, 59 Boulevard Louis Pinel, 69677 Bron Cedex, France.
authors: Coralie
authors: C
authors: Bouchiat
authors: CIRI, International Center for Infectiology Research, Inserm U1111, Université Lyon 1, Ecole Normale Supérieure de Lyon, CNRS UMR5308, 7 rue Guillaume Paradin, 69008 Lyon, France.
authors: Karen
authors: K
authors: Moreau
authors: Université de Lyon, Université Lyon 1, CNRS, UMR5558, Laboratoire de Biométrie et Biologie Evolutive, F-69622 Villeurbanne, France.
authors: Sébastien
authors: S
authors: Devillard
authors: CIRI, International Center for Infectiology Research, Inserm U1111, Université Lyon 1, Ecole Normale Supérieure de Lyon, CNRS UMR5308, 7 rue Guillaume Paradin, 69008 Lyon, France; Centre National de Référence des Staphylocoques, 59 Boulevard Louis Pinel, 69677 Bron Cedex, France.
authors: Jean-Philippe
authors: JP
authors: Rasigade
authors: CIRI, International Center for Infectiology Research, Inserm U1111, Université Lyon 1, Ecole Normale Supérieure de Lyon, CNRS UMR5308, 7 rue Guillaume Paradin, 69008 Lyon, France.
authors: Amandine
authors: A
authors: Mosnier
authors: CIRI, International Center for Infectiology Research, Inserm U1111, Université Lyon 1, Ecole Normale Supérieure de Lyon, CNRS UMR5308, 7 rue Guillaume Paradin, 69008 Lyon, France.
authors: Tom
authors: T
authors: Geissmann
authors: Laboratoire de Bactériologie, Centre de Biologie Est, Hospices Civils de Lyon, 59 Boulevard Louis Pinel, 69677 Bron Cedex, France; CIRI, International Center for Infectiology Research, Inserm U1111, Université Lyon 1, Ecole Normale Supérieure de Lyon, CNRS UMR5308, 7 rue Guillaume Paradin, 69008 Lyon, France; Centre National de Référence des Staphylocoques, 59 Boulevard Louis Pinel, 69677 Bron Cedex, France.
authors: Michèle
authors: M
authors: Bes
authors: Laboratoire de Bactériologie, Centre de Biologie Est, Hospices Civils de Lyon, 59 Boulevard Louis Pinel, 69677 Bron Cedex, France; CIRI, International Center for Infectiology Research, Inserm U1111, Université Lyon 1, Ecole Normale Supérieure de Lyon, CNRS UMR5308, 7 rue Guillaume Paradin, 69008 Lyon, France; Centre National de Référence des Staphylocoques, 59 Boulevard Louis Pinel, 69677 Bron Cedex, France.
authors: Anne
authors: A
authors: Tristan
authors: CIRI, International Center for Infectiology Research, Inserm U1111, Université Lyon 1, Ecole Normale Supérieure de Lyon, CNRS UMR5308, 7 rue Guillaume Paradin, 69008 Lyon, France; Centre National de Référence des Staphylocoques, 59 Boulevard Louis Pinel, 69677 Bron Cedex, France.
authors: Gérard
authors: G
authors: Lina
authors: CIRI, International Center for Infectiology Research, Inserm U1111, Université Lyon 1, Ecole Normale Supérieure de Lyon, CNRS UMR5308, 7 rue Guillaume Paradin, 69008 Lyon, France; Centre National de Référence des Staphylocoques, 59 Boulevard Louis Pinel, 69677 Bron Cedex, France.
authors: Frédéric
authors: F
authors: Laurent
authors: Service de Maladies Infectieuses, CHU de Dijon, 14 rue Gaffarel, 21079 Dijon Cedex, France.
authors: Lionel
authors: L
authors: Piroth
authors: Laboratoire de Bactériologie, CHU de Nancy, 29 avenue du Maréchal de Lattre de Tassigny, 54035 Nancy, France.
authors: Nejla
authors: N
authors: Aissa
authors: Centre d'Investigation Clinique, Inserm CIC 1425, IAME, Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, 75018 Paris, France.
authors: Xavier
authors: X
authors: Duval
authors: Service des Maladies Infectieuses et Tropicales, CHU de Montpellier, Hôpital Gui de Chauliac, 34000 Montpellier, France.
authors: Vincent
authors: V
authors: Le Moing
authors: Laboratoire de Bactériologie, Centre de Biologie Est, Hospices Civils de Lyon, 59 Boulevard Louis Pinel, 69677 Bron Cedex, France; CIRI, International Center for Infectiology Research, Inserm U1111, Université Lyon 1, Ecole Normale Supérieure de Lyon, CNRS UMR5308, 7 rue Guillaume Paradin, 69008 Lyon, France; Centre National de Référence des Staphylocoques, 59 Boulevard Louis Pinel, 69677 Bron Cedex, France. Electronic address: francois.vandenesch@univ-lyon1.fr.
authors: François
authors: F
authors: Vandenesch
mesh_terms: D016470:Bacteremia / Q000382:microbiology*; D017714:Community-Acquired Infections; D004697:Endocarditis, Bacterial / Q000382:microbiology*; D005798:Genes, Bacterial; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D010641:Phenotype; D015203:Reproducibility of Results; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D005819:Genetic Markers
keywords: Bacteremia; DAPC; Genetic distinction; Infective endocarditis; Staphylococcus aureus