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2594. Biofilm-Dispersed Staphylococcus aureus Exhibits a Distinct agr-Independent Host Interaction

BACKGROUND: Staphylococcus aureus biofilms are a common cause of persistent, life-threatening infections. Dispersal of S. aureus cells from established biofilm-based infections is crucial for dissemination within the host, but is poorly understood. We tested the hypothesis that biofilm dispersed S....

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Detalles Bibliográficos
Autores principales: Chang, Spencer, Fowler, Vance G, Sharma-Kuinkel, Batu K, Medie, Felix, Park, Larry, Zheng, Yue, Otto, Michael, Horswill, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811026/
http://dx.doi.org/10.1093/ofid/ofz360.2272
Descripción
Sumario:BACKGROUND: Staphylococcus aureus biofilms are a common cause of persistent, life-threatening infections. Dispersal of S. aureus cells from established biofilm-based infections is crucial for dissemination within the host, but is poorly understood. We tested the hypothesis that biofilm dispersed S. aureus cells have distinct physiology from planktonic cells and are better equipped to evade host immunity in an agr-dependent manner. METHODS: Primary murine bone marrow-derived macrophages (BMDMs) were infected with planktonic and biofilm dispersed cells from S. aureus USA300 LAC wild type (WT) and USA300 LAC-agr knockout (KO). Biofilm dispersed cells were collected via glucose deprivation. Gentamicin protection assays were used to enumerate phagocytosed bacteria and fluorescence microscopy to quantify macrophage viability. A 26-plex immunoassay was used to screen for cytokines and chemokines. Reversed phase high-performance liquid chromatography was used to measure relative phenol-soluble modulin (PSM) levels from macrophage co-cultures. RESULTS: Compared with planktonic cells, biofilm-dispersed cells in both S. aureus WT and KO backgrounds exhibited: (1) ~10-fold less phagocytosis by BMDMs (p = 0.0003; Figure 1); (2) increased macrophage killing (23% vs. 8%; p = 0.0038; Figure 2); (3) stronger pro- (e.g., IFN-y, IL-2, IL-6, IL-17; Figure 3A) and anti- (e.g., IL-10, IL-4, IL-22; Figure 3B) inflammatory cytokine responses from macrophages (P < 0.05 for all); (4) significantly higher δ toxin PSM production (P = 0.0090; Figure 4) in WT background only. CONCLUSION: S. aureus biofilm dispersed cells are physiologically distinct from planktonic cells and have a unique interaction with the host immune system. Dispersed cells are more resistant to phagocytosis, have a greater propensity to kill macrophages, and mount stronger pro- and anti-inflammatory responses in an agr-independent manner. Dispersed cells also have the ability to produce more δ toxin PSM via well-known agr-dependent pathways. [Image: see text] [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.