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

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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.

OriginalsprogEngelsk
Artikelnummer120775
TidsskriftBiomaterials
Vol/bind275
Antal sider13
ISSN0142-9612
DOI
StatusUdgivet - aug. 2021

Bibliografisk note

Funding Information:
This work was supported by National Institute of Allergy and Infectious Diseases award 1R01AI149591 and National Institute of General Medical Sciences award U54GM115371 to J.M.V. at Montana State University. Work at the University of Calgary was supported by Canadian Institutes of Health Research Foundation grant #FDN-143248 to P.K. Work at the University of Copenhagen was supported by the Lundbeck Foundation to T.B. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2021 Elsevier Ltd

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