4.8 Article

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

期刊

BIOMATERIALS
卷 275, 期 -, 页码 -

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.120775

关键词

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

资金

  1. National Institute of Allergy and Infectious Diseases award [1R01AI149591]
  2. National Institute of General Medical Sciences [U54GM115371]
  3. Canadian Institutes of Health Research Foundation [FDN143248]
  4. Lund-beck Foundation

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Biofilms formed on implanted medical devices lead to persistent infections, but the mechanisms by which bacteria evade immune clearance in the early stages are not well understood. Research shows that bacterial aggregates on implant surfaces can resist neutrophil killing, allowing them to establish biofilms and acquire tolerance to immune clearance.
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 (similar to 50 mu m(2)) 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.

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