Selective Chemical Inhibition of agr Quorum Sensing in Staphylococcus aureus Promotes Host Defense with Minimal Impact on Resistance
Figure 5
Savirin promotes agr-dependent host defense in vivo and in vitro.
(A) Effect of 10 µg of savirin vs. vehicle on infection with 2×107 LAC AH 1677 (agr::P3 driving yfp) of Nox2−/− mice (n = 8 per group) in an air-pouch model 24 hrs after infection. Parameters shown include the fluorescence of bacteria in a lavage of the pouch, weight loss, and bacterial burden in the pouch and in the kidney. (B) Effect of 10 µg savirin vs vehicle on infection with 5×107 LAC Δagr of wild-type C57BL/6 mice (n = 4 per group) in an air-pouch model 24 hr after infection. Parameters shown include weight loss and bacterial burden in a lavage of the pouch and kidney. (C) Effect of savirin (5 µg) vs vehicle injected at the time of infection with 4×107 LAC agr+ or Δagr subcutaneously in the flank (n = 10–15 mice per group) of immunocompetent hairless SKH1 mice. Parameters shown include images of the infection sites at day 3; abscess area for agr+ infected mice; ulcer area for agr+ infected mice; weight loss over 3 days for agr+ infected mice; bacterial burden measured as CFU from the skin of agr+ infected mice at days 3 and 7; and bacterial burden measured as CFU from the spleen of agr+ infected mice at days 3 and 7. (D) Effect of delayed addition of savirin in vitro and in vivo. Parameters shown include the in vitro effect of savirin (5 µg ml−1) added at 3 hrs on RNAIII levels at 5 hr. **p<0.01 by two tailed Student's t test and savirin (5 µg) vs. vehicle injected 24 and 48 hrs after infection (n = 12–13 mice per group), depicting abscess area (arrows indicate timing of savirin/vehicle injection), ulcer size, bacterial burden in the skin at day 7, and bacterial burden in the spleen at day 7. All data from mouse infection represented as mean ±SEM ***p<0.001 **p<0.01, *p<0.05 by two-tailed Mann-Whitney U test.