Figure 1.

Ring-Fused 2-Pyridones Inhibit L. monocytogenes Uptake by Cultured Cells

(A) Relative uptake (%) compared with control as determined by viable count measurements. L. monocytogenes strain EGDe (WT) treated with compounds 1–3 at the indicated concentrations (10 μM, black bars; 1 μM, white bars) was allowed to infect HeLa cells for 1.5 hr. All samples were correlated to the DMSO control (C, gray bar), which was arbitrarily set at 100%. Error bars show SDs. Significance was tested using Student's t test (two-tailed, significant differences are shown by asterisks; *p < 0.05; **p < 0.01, and ***p < 0.001) and Dunnett's test (significant differences are shown by #). See also Figure S1.

(B) Time-course infection dynamics of L. monocytogenes harboring PrfA_WT or PrfA_G145S after treatment with compound 2. Caco-2 cells were infected with L. monocytogenes strains carrying PrfA_WT (left panels) or PrfA_G145S (right panels) on the chromosome in the presence of DMSO (C) or compound 2 (50 μM). The amount of intracellular bacteria was measured using viable counts at indicated time points post infection and divided by the bacterial load used in the infection (prior to antibiotic treatment) arbitrarily set as % (n = 3). It should be noted that infection of Caco-2 cells with a strain harboring PrfA_G145S is more effective than with a strain carrying PrfA_WT. Error bars show SDs. Significance was tested using Student's t test (two-tailed, significant differences are shown by asterisks; *p < 0.05) and Dunnett's test (significant differences to the control are shown by #).