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Wonbeom Paik, Mallory L Paynich, Francis Alonzo, Katherine L Knight, Protection from Staphylococcus aureus sepsis by bacterial exopolysaccharide, The Journal of Immunology, Volume 198, Issue Supplement_1, May 2017, Page 131.12, https://doi.org/10.4049/jimmunol.198.Supp.131.12
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Abstract
Sepsis is the most severe presentation of systemic infection with up to 50% mortality rates. The leading etiological agent of sepsis is a Gram-positive bacterium, Staphylococcus aureus. Antibiotics are the only effective therapy for S. aureus sepsis, and widespread resistance to multiple antibiotics is a major concern. Novel therapeutic agents for sepsis are critically needed. We previously showed that exopolysaccharides (EPS) derived from a probiotic bacterium, Bacillus subtilis, protects hosts from inflammatory disease by the induction of anti-inflammatory M2 macrophages. Using a murine systemic infection model, we tested if EPS also has therapeutic potential for S. aureus sepsis. We treated mice with EPS prior to infection with S. aureus and found that weight loss, serum proinflammatory cytokine levels, and bacterial burden in the liver were mitigated compared to vehicle-treated controls. We also found that compared to cells from vehicle-treated mice, peritoneal cells from EPS-treated mice suppress growth of serum-opsonized S. aureus in vitro. We purified peritoneal F4/80-positive macrophages from EPS-treated mice and found that they were responsible for suppressing S. aureus growth by peritoneal cells. We confirmed this by depletion of macrophages from mice using clodronate-loaded liposomes, which mitigated suppression of S. aureus growth by peritoneal cells from EPS-treated mice. We suggest that B. subtilis-derived EPS may be useful for prevention and/or treatment of S. aureus sepsis.
