Delayed neutrophil recruitment allows nascent Staphylococcus aureus biofilm formation and immune evasion

Brian A. Pettygrove, Rachel M. Kratofil, Maria Alhede, Peter Jensen, Michelle Newton, Klaus Qvortrup, Kyler B. Pallister, Thomas Bjarnsholt, Paul Kubes, Jovanka M. Voyich, Philip S. Stewart*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Biofilms that form on implanted medical devices cause recalcitrant infections. The early events enabling contaminating bacteria to evade immune clearance, before a mature biofilm is established, are poorly understood. Live imaging in vitro demonstrated that Staphylococcus aureus sparsely inoculated on an abiotic surface can go undiscovered by human neutrophils, grow, and form aggregates. Small (~50 μm2) aggregates of attached bacteria resisted killing by human neutrophils, resulting in neutrophil lysis and bacterial persistence. In vivo, neutrophil recruitment to a peritoneal implant was spatially heterogenous, with some bacterial aggregates remaining undiscovered by neutrophils after 24 h. Intravital imaging in mouse skin revealed that attached S. aureus aggregates grew and remained undiscovered by neutrophils for up to 3 h. These results suggest a model in which delayed recruitment of neutrophils to an abiotic implant presents a critical window in which bacteria establish a nascent biofilm and acquire tolerance to neutrophil killing.

Original languageEnglish
Article number120775
JournalBiomaterials
Volume275
Number of pages13
ISSN0142-9612
DOIs
Publication statusPublished - Aug 2021

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Ltd

Keywords

  • Biofilm
  • Implant-associated infection
  • Microscopy
  • Neutrophil
  • Staphylococcus aureus
  • Up to 10)

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