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Front. Cell. Infect. Microbiol. | doi: 10.3389/fcimb.2018.00187

Staphylococcus aureus CC30 lineage and absence of sed,j,r-harboring plasmid predict embolism in infective endocarditis

 Jean-Philippe Rasigade1, 2*,  Amélie Leclère3, 4, François Alla5, 6, Adrien Tessier3, 4,  Michèle Bès1, 2, Catherine Lechiche7,  Veronique Vernet Garnier8, 9,  Cédric Laouénan3, 4, 10,  Francois Vandenesch1, 2 and Catherine Leport3, 4, 11
  • 1CIRI INSERM U1111, Université de Lyon, France
  • 2Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, France
  • 3Université Sorbonne Paris Cité, France
  • 4INSERM U1137 Infection, Antimicrobiens, Modélisation, Evolution, France
  • 5CIC-1433 Epidémiologie clinique, Centre Hospitalier Universitaire de Nancy, France
  • 6EA4360 Apemac, Université de Lorraine, France
  • 7Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Nîmes, France
  • 8Faculté de Médecine EA 4687, Université de Reims Champagne Ardenne, France
  • 9Laboratoire de Bactériologie, Centre Hospitalier Universitaire de Reims, France
  • 10Service de Biostatistiques, Hôpital Bichat-Claude-Bernard, France
  • 11Unité de Coordination du risque épidémique et biologique, Assistance Publique Hopitaux De Paris (AP-HP), France

Staphylococcus aureus induces severe infective endocarditis (IE) where embolic complications are a major cause of death. Risk factors for embolism have been reported such as a younger age or larger IE vegetations, while methicillin resistance conferred by the mecA gene appeared as a protective factor. It is unclear, however, whether embolism is influenced by other S. aureus characteristics such as clonal complex (CC) or virulence pattern. We examined clinical and microbiological predictors of embolism in a prospective multicentric cohort of 98 French patients with monomicrobial S. aureus IE. The genomic contents of causative isolates were characterized using DNA array. To preserve statistical power, genotypic predictors were restricted to CC, secreted virulence factors and virulence regulators. Multivariate regularized logistic regression identified three independent predictors of embolism. Patients at higher risk were younger than the cohort median age of 62.5y (adjusted odds ratio [OR] 0.14; 95% confidence interval [CI] 0.05 to 0.36). S. aureus characteristics predicting embolism were a CC30 genetic background (adjusted OR 9.734; 95% CI 1.53 to 192.8) and the absence of pIB485-like plasmid-borne enterotoxin-encoding genes sed, sej and ser (sedjr; adjusted OR 0.07; 95% CI 0.004 to 0.457). CC30 S. aureus has been repeatedly reported to exhibit enhanced fitness in bloodstream infections, which might impact its ability to cause embolism. sedjr-encoded enterotoxins, whose superantigenic activity is unlikely to protect against embolism, possibly acted as a proxy to others genes of the pIB485-like plasmid found in genetically unrelated isolates from mostly embolism-free patients. mecA did not independently predict embolism but was strongly associated with sedjr. This mecA-sedjr association might have driven previous reports of a negative association of mecA and embolism. Collectively, our results suggest that the influence of S. aureus genotypic features on the risk of embolism may be stronger than previously suspected and independent of clinical risk factors.

Keywords: Staphylococcus aureus, MRSA, Infective endocarditis, Stroke, CC30, superantigen, Plasmid, Enterotoxins

Received: 18 Dec 2017; Accepted: 14 May 2018.

Edited by:

Martin J. McGavin, University of Western Ontario, Canada

Reviewed by:

Beatrix Stessl, Veterinärmedizinische Universität Wien, Austria
William Schwan, University of Wisconsin–La Crosse, United States  

Copyright: © 2018 Rasigade, Leclère, Alla, Tessier, Bès, Lechiche, Vernet Garnier, Laouénan, Vandenesch and Leport. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Jean-Philippe Rasigade, Université de Lyon, CIRI INSERM U1111, Lyon, France,