Non-synonymous mutations that accumulate in <i>C. glabrata</i> during the evolution of echinocandin resistance in a human host.

<p><i>C. glabrata</i> clinical isolates display a step-wise increase in caspofungin resistance in a Minimum Inhibitory Concentration (MIC) assay. Isolates are arranged in the same order as they were recovered from the patient, where isolate A was recovered pre-treatment and isolate G was recovered after multiple rounds of caspofungin treatment. Assays were performed in RPMI medium with 2% glucose at 30°C for 72 hours. Optical densities were averaged for duplicate measurements and normalized relative to caspofungin-free controls (see color bar). The nine non-synonymous mutations identified in isolate G compared to isolate A using whole genome sequencing (marked in red) were mapped across isolates B to F using Sanger sequencing. Mutations in <i>MOH1</i>, <i>GPH1</i>, <i>CDC6</i>, and <i>TCB1/2</i> occur between isolates B and C, which correspond to a small increase in echinocandin resistance, outlined in blue boxes. Mutations in <i>DOT6</i>, <i>MRPL11</i>, <i>FKS2</i>, and <i>SUI2</i> correspond to a sharp increase in echinocandin resistance, outlined in black boxes.