Inhibitors of Pathogen Intercellular Signals as Selective Anti-Infective Compounds
Figure 4
The AA Analogs Promote Survival of B+I Mice to PA14 Pathogenesis, and Restrict In Vivo HHQ Production
(A) PA14-infected mice were injected 6 h post-B+I with 6FABA, 6CABA, or 4CABA. Mice infected with pqsA− cells served as an additional control group. Data were averaged for a minimum of two independent experiments, with n(PA14) = 40; n(PA14/6FABA) = 36; n(PA14/6CABA) = 30; n(PA14/4CABA) = 20 and n(pqsA−) = 20. Standard deviations were <20% for the time points between 0 and 4 d, and <12% thereafter. Cox proportional hazards regression showed that mouse mortality due to PA14 infection was significantly reduced by injection with 6FABA (hazard ratio = 0.398, p = 5.6e-04), 6CABA (hazard ratio = 0.397, p = 1.2e-03), and 4CABA (hazard ratio = 0.325, P = 1.8e-03), compared with control saline; pqsA− virulence was highly attenuated (hazard ratio = 0.118, p = 9.1e-06).
(B) HHQ levels (μg/mg) at 12 h post-B+I for rectus adbominus muscle directly underlying the infection site in untreated B+I mice, and for mice treated 6 h post-B+I with 6FABA, 6CABA, or 4CABA. n = 5 for each experimental condition. The t-test (p = 0.011) and Wilcoxon rank sum test (p = 0.03) showed that the difference in HHQ levels between control and 4CABA-treated mice was statistically significant.