All Staphylococcus aureus bacteraemia-inducing strains can cause infective endocarditis: Results of GWAS and experimental animal studies - 28/01/23

Doi : 10.1016/j.jinf.2022.12.028

Sylvère Bastien ^a, Severien Meyers ^b,^{^{1
equal authorship}}, Wilmara Salgado-Pabón ^c,^{^{1
equal authorship}}, Stefano G. Giulieri ^d,^e, Jean-Phillipe Rasigade ^a,^f, Laurens Liesenborghs ^b, Kyle J. Kinney ^g, Florence Couzon ^a, Patricia Martins-Simoes ^a,^f, Vincent Le Moing ^h, Xavier Duval ^i,^j, Natasha E Holmes ^e, Niels Eske Bruun ^k,^l, Robert Skov ^m, Benjamin P Howden ^d,^e, Vance G. Fowler ^n,^o, Peter Verhamme ^b, Paal Skytt Andersen ^m, Coralie Bouchiat ^a,^f,^{^{2
equal senior authorship}}, Karen Moreau ^a,^{^{2
equal senior authorship}}, François Vandenesch ^a,^f,^{^{2
equal senior authorship},}^⁎
^a CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France
^b Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium
^c Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, USA
^d Department of Microbiology and Immunology and Department of Infectious Diseases, The University of Melbourne at the Doherty Institute for Infection and Immunity; Victorian Infectious Disease Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
^e Department of Infectious Diseases, Austin Health, Heidelberg, Australia
^f Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, F-69004, Lyon, France
^g Department of Microbiology and Immunology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA
^h Service de Maladies Infectieuses, CHU de Montpellier, France
ⁱ Hôpital Bichat Claude Bernard, AP-HP, Paris, France
^j Inserm CIC 1425, Inserm UMR-1137 IAME, Cité Paris University, UFR de Médecine-Bichat, Paris, France
^k Clinical Institute, Copenhagen and Aalborg University, Aalborg, Denmark
^l Department of Cardiology, Zealand University Hospital Roskilde, Roskilde, Zealand, Denmark
^m Department of Bacteria, Parasites, and Fungi, Statens Serum Institut, Copenhagen, Denmark
ⁿ Duke University Medical Center, Durham, NC USA
^o Duke Clinical Research Institute, Durham, NC USA

^⁎Corresponding author.

Highlights

•	Staphylococcus aureus bacteraemia (SAB) can lead to infective endocarditis (IE).
•	Specific traits of IE-causing strains versus SAB-only are questioned.
•	GWAS from IE and SAB-only strains does not discriminate the 2 groups.
•	In murine and rabbit IE models, IE and SAB-only strains behave in the same way.

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Summary

Objectives

We aimed at determining whether specific S. aureus strains cause infective endocarditis (IE) in the course of Staphylococcus aureus bacteraemia (SAB).

Methods

A genome-wide association study (GWAS) including 924 S. aureus genomes from IE (274) and non-IE (650) SAB patients from international cohorts was conducted, and a subset of strains was tested with two experimental animal models of IE, one investigating the early step of bacterial adhesion to inflamed mice valves, the second evaluating the local and systemic developmental process of IE on mechanically-damaged rabbit valves.

Results

The genetic profile of S. aureus IE and non-IE SAB strains did not differ when considering single nucleotide polymorphisms, coding sequences, and k-mers analysed in GWAS. In the murine inflammation-induced IE model, no difference was observed between IE and non-IE SAB strains both in terms of adhesion to the cardiac valves and in the propensity to cause IE; in the mechanical IE-induced rabbit model, there was no difference between IE and non-IE SAB strains regarding the vegetation size and CFU.

Conclusion

All strains of S. aureus isolated from SAB patients must be considered as capable of causing this common and lethal infection once they have accessed the bloodstream.

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Keyword : Infective endocarditis, Bacteraemia, Genome-wide association study, Experimental animal model, Staphylococcus aureus

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Vol 86 - N° 2

P. 123-133 - février 2023 Retour au numéro

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All Staphylococcus aureus bacteraemia-inducing strains can cause infective endocarditis: Results of GWAS and experimental animal studies - 28/01/23

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