Figure 1. 2-AA enhances survival following BI.

(A) Mice were injected with 2-AA (6.75 mg/kg mice) or PBS 6 h (n = 20), 2 d (n = 20), 4 d (n = 20), 8 d (n = 20), or 30 d (n = 20) prior to BI with PA14. The data shown are averages of two independent experiments. Significance of survival rate differences was determined using the Kaplan-Meier method, with a hazard ratio of 1.8932 (95% CI, 1.0664–6.0718). Infection (−) drastically reduced survival relative to (2-AA W/O BI) controls (p = 0.03). Delivery of 2-AA 4 d before BI (red) had a particularly powerful influence on survival versus mice not pretreated with 2-AA (p = 0.03). A less remarkable, but still significant, survival benefit was also observed in BI mice pre-exposed to 2-AA 6 h, 2 d, 8 d, or 30 d before BI (all p = 0.03 vs. non-infected 2-AA exposed controls). (B) Relative to the effects observed with 2-AA (n = 20), 4 d pretreatment with the 2-AA analogs 4-AA (n = 8; p = 0.03), 2-NA (n = 8; p = 0.03), or MA (n = 8; p = 0.03), or the 2-AA metabolite 3OH-2-AA (n = 8; p = 0.03) prior to PA14 infection had weak, though still statistically significant, positive effects on survival after infection. Significance of survival rate differences was calculated as in A. (C) Bacterial loads in the local muscle 7 d post-BI were significantly higher in mice pretreated with 2-AA 4 d before BI (n = 7) than in control mice subjected to BI without 2-AA pretreatment (n = 7; p<0.05, Kruskal-Wallis test). CFU data are presented on a log₁₀ scale. (D) CFU counts at the site of infection in mice 11 d postinfection. The 2-AA treated mice showed proliferation and higher counts than mice that were not treated with 2-AA. (n = 6; p<0.001, Kruskal-Wallis test). CFU data are presented on a log₁₀ scale.