Journal Article Ahead of print
PubMed: 42156734 DOI: 10.1038/s41467-026-72657-5
Genetic determinants of Staphylococcus aureus adhesion shape virulence trade-offs in bacteremia.
Nat Commun
Authors: Francesc Coll, Paula Rożen, Monika Budnik, Halina Marchel, Joan A Geoghegan, Katarzyna Holcman, Magdalena Mizia-Szubryt, Adrianna Berger-Kucza, Aldona Olechowska-Jarząb, Karol Makuch, Coralie Bouchiat-Sarabi, François Vandenesch, Marta Zapotoczna
Affiliations
- Applied Microbial Genomics Unit, Department of Molecular Basis of Disease, Biomedicine Institute of Valencia (IBV), Spanish Research Council (CSIC), Valencia, Spain. Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
- Laboratory of Infection Biology, Biological and Chemical Research Centre, University of Warsaw, Warsaw, Poland.
- 1st Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
- Department of Dental Microbiology, Medical University of Warsaw, Warsaw, Poland. Department of Microbiology, Central Clinical Hospital, University Clinical Centre, Medical University of Warsaw, Warsaw, Poland.
- Department of Microbes, Infection and Microbiomes, College of Medicine and Health & Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK.
- Department of Cardiac and Vascular Diseases, Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland.
- Department of Cardiac and Vascular Diseases, St. John Paul II Hospital, Kraków, Poland.
- Department of Nuclear Medicine, St. John Paul II Hospital, Kraków, Poland.
- 1st Department of Cardiology, Medical University of Silesia, Katowice, Poland.
- Department of Microbiology, University Hospital in Kraków, Kraków, Poland.
- Institute of Physical Chemistry, Polish Academy of Sciences, Warszawa, Poland.
- CIRI, Center for Integrative Research in Infectious Diseases and Immunology, INSERM U1111, CNRS UMR5308, University of Lyon, ENS Lyon, Lyon, France.
- Centre National de Référence des Staphylocoques, Infectious Agents Institute, Hospices Civils de Lyon, Lyon, France.
- Laboratory of Infection Biology, Biological and Chemical Research Centre, University of Warsaw, Warsaw, Poland.
Abstract
Staphylococcus aureus is a major cause of bloodstream infections, but how variation between strains in their ability to adhere to host proteins influences disease severity remains unclear. Here we show that adhesion is a highly variable and biologically important trait in 236 phylogenetically diverse, representative bacteremia isolates profiled for binding to fibrinogen and fibronectin and analysed together with bacterial whole-genome sequences and matched patients' clinical data. Stronger fibrinogen-binding, particularly in strains lacking α-toxin, correlates with heightened systemic inflammation (r = 0.401, P = 0.0001) but lower mortality (16.6% vs. 38.7%, P = 0.018), linking bacterial adhesion to distinct clinical outcomes. Genome-wide association analyses identify top-associated variants in genes encoding known adhesins (clfA, fnbA, fnbB, ebh), other surface factors (spa, sdrH), mobile genetic elements, and novel loci (csbB, glcA), although not statistically significant. Functional analyses reveal that protein A limits ClfA-dependent fibrinogen binding through steric hindrance, CsbB interferes with ClfA exposure on bacterial surface, and GlcA enhances fibronectin binding via metabolic regulation. These findings define adhesion as a polygenic, evolutionarily variable trait and suggest that highly-adhesive, α-toxin-defective isolates promote inflammatory but self-limiting infections, whereas weakly adhesive, high-toxicity strains favour immune evasion and severe disease.
MeSH
Bacteremia, Tissue Adhesions, Staphylococcus, Fibrinogen, Adhesives, Staphylococcus Aureus, Fibronectins, Virulence, Infections