FIG 4.
In vivo susceptibilities of isogenic mutants derived from parental strain (SSCL). The parental strain and the four isogenic mutant strains (RRMH2, RSMH1, SRMH1, and RRMHO2) were evaluated for high (AUC500) and standard (AUC100) doses of anidulafungin (ANI) (A), caspofungin (CAS) (B), and micafungin (MICA) (C) and compared to placebo control. The treatment groups consisted of six mice and the control groups consisted of eight mice. The CFU counts per ml kidney homogenate are depicted after the end of treatment. The limit of detection (LoD) and median with interquartile range are indicated in each graph. The statistic is based on the Kruskal-Wallis test and Dunnett's multiple comparison tests, with statistical significances given as P < 0.5 (*), P < 0.01 (**), and P < 0.001 (***); outliers (maximum of one per control group) were removed for calculation only (CFU ≤ 100 in the placebo-treated groups). The strains carry the following mutations in their FKS gene: RRMH2 heterozygous double mutation (R647R/G and P649P/L), RSMH1 (R647R/G) and SRMH1 (P649P/L) heterozygous single mutations, and RRMHO2 homozygous double mutation (R647G and P649L).