FIG 1.
Phenomena potentially underlying low-level PZA-R monoresistance conferred by clpC1Val63Ala. Curves depict theoretical probability density functions of MICs obtained for a given isolate. (A) Epistasis. In the epistatic scenario, clpC1Val63Ala alone confers low-level resistance, invariably below the 100-mg/liter critical concentration, but some isolates (reds) harbor additional mutations that confer higher-level PZA-R through additive or synergistic interaction with clpC1Val63Ala. (B) Near-critical concentration MIC. In this scenario, low-level PZA resistance conferred by clpC1Val63Ala alone sometimes exceeds the 100-mg/liter cutoff, due to nongenetic factors contributing to MIC variance (30, 31), such as inoculum size (32), growth medium, or interlaboratory variation (33). The phenomena depicted in panels A and B are not mutually exclusive and could both be at work.