FIGURE 4.

Reversal of β-lactam resistance in MRSA strain COL. (A) The diameter of the clearing zones in the disc diffusion assay was measured and the ratio of the diameters of the inhibition zones in the presence and absence of compound were used to calculate a sensitizing score for each compound/β-lactam combination as described in the Methods section. The compounds are listed according to their ability to stimulate growth of the clpX mutant from bottom to top. (B) The scores across all antibiotics are added to give a total synergy score for each compound. The score is plotted against the fold change in growth of clpX in the presence of compound, together with a linear regression line (R ² = 0.62) (C) Synergy between imipenem and the three compounds with highest sensitizing scores was evaluated by performing microdilution checkerboard analyses against the highly resistant MRSA strain, COL. The extent of inhibition is shown as a heat plot.