A novel in vitro model for haematogenous spreading of S. aureus device biofilms demonstrating clumping dispersal as an advantageous dissemination mechanism

Rasmus Birkholm Grønnemose, Kirstine Lindhardt Sæderup (Madsen), Hans Jørn Kolmos, Søren Hansen, Cecilie Antoinette Asferg, Karina Juhl Rasmussen, Yaseelan Palarasah, Thomas Emil Andersen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Staphylococcus aureus is able to disseminate from vascular device biofilms to the blood and organs, resulting in life-threatening infections such as endocarditis. The mechanisms behind spreading are largely unknown, especially how the bacterium escapes immune effectors and antibiotics in the process. Using an in vitro catheter infection model, we studied S. aureus biofilm growth, late-stage dispersal, and reattachment to downstream endothelial cell layers. The ability of the released biofilm material to resist host response and disseminate in vivo was furthermore studied in whole blood and phagocyte survival assays and in a short-term murine infection model. We found that S. aureus biofilms formed in flow of human plasma release biofilm thromboemboli with embedded bacteria and bacteria-secreted polysaccharides. The emboli disseminate as antibiotic and immune resistant vehicles that hold the ability to adhere to and initiate colonisation of endothelial cell layers under flow. In vivo experiments showed that the released biofilm material reached the heart similarly as ordinary broth-grown bacteria but also that clumps to some extend were trapped in the lungs. The clumping dispersal of S. aureus from in vivo-like vascular biofilms and their specific properties demonstrated here help explain the pathophysiology associated with S. aureus bloodstream infections.

Original languageEnglish
Article numbere12785
JournalCellular Microbiology
Volume19
Issue number12
Number of pages13
ISSN1462-5814
DOIs
Publication statusPublished - Dec 2017

Keywords

  • biofilm
  • infection
  • microbial-cell interaction
  • staphylococci
  • Staphylococcal Infections/microbiology
  • Blood/microbiology
  • Staphylococcus aureus/physiology
  • Phagocytes/microbiology
  • Biofilms/growth & development
  • Microbial Viability
  • Thromboembolism/microbiology
  • Endothelial Cells/microbiology
  • Bacterial Adhesion
  • Animals
  • Mice
  • Catheter-Related Infections/microbiology
  • Disease Models, Animal

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