TABLE 1.

In vitro whole-cell susceptibility (MIC) and GS inhibition profiles (IC50) for ECD of the C. albicans strains included in the studyh

StrainFKS1 genotypeFKS1 HS1aFKS1 HS2bMIC (μg/ml)cIC50 (ng/ml)d
ANFCSFMCFANFCSFMCF
No serum50% serumNo serum50% serumNo serum50% serum
SC5314eWTWTWT0.080.500.420.500.050.500.89 (11.41)3.88 (64.13)58.2 (198.6)
36082eWTWTWT0.030.120.210.250.031.001.51 (20.1)0.9 (16.5)10.2 (31.3)
90028eWTWTWT0.030.250.210.250.030.501.83 (25.4)0.5 (9.4)18.8 (60.1)
1002fWTWTWT0.060.440.330.500.040.507.961.7553.34
3107fWTWTWT0.030.250.250.330.030.503.123.6214.72
3795fWTWTWT0.060.440.330.500.030.506.761.4438.89
119fT1921CF641LWT0.162.002.008.000.338.0011.310.03183.6
177fT1922CF641SWT0.834.004.0016.01.0016.0262210911441
2762fT1922CF641SWT1.004.003.338.001.0016.010859101693
205fT1933CS645PWT1.338.008.008.004.008.00989245.41085
5415fT1933CS645PWT2.008.008.008.004.008.001152698.11254
89fC1934AS645YWT2.008.008.008.004.008.00273920752533
85fC1934TS645FWT2.008.004.008.002.678.00787459.1449.8
149fG1942TD648YWT0.834.002.674.000.834.0093.368.22375.5
122fC1946AP649HWT0.678.004.004.000.834.0049182.66924.6
121fG4082AWTR1361H0.258.002.008.000.258.0075.9933.72498.2
194fC1934T/G4082RS645FR1361R/H4.008.004.008.002.678.00782530.71765
90fG4082RWTR1361R/H0.254.001.004.000.504.0040.6 (1.01)20.43 (2.05)77.39 (22.5)
A15gT1933YS645S/PWT0.502.004.008.000.502.00128.7 (0.39)218.1 (4.19)177.3 (35.5)
A15-10gT1933CS645PWT4.008.008.0016.04.008.00901322.41194
  • a HS1, hot spot 1 (FKS1 amino acids 641 and 649). The wild-type sequence is 41-FLTLSLRDP-649.

  • b HS2, hot spot 2 (FKS1 amino acids 1357 and 1364). The wild-type sequence is 1357-DWIRRTYL-1364.

  • c Shown are geometric means (three repetitions on three separate days).

  • d IC50 values obtained using trapped 1,3-β-d-glucan synthase enzyme. Shown are arithmetic means (three repetitions on three separate days). IC50 values obtained using crude membranes (strains SC5314, 36082, and 90028) and IC501 (susceptible allele) using a two-site competition-fitting algorithm (strains 90 and A15) are shown in parentheses.

  • e Control strains.

  • f Clinical strains.

  • g Spontaneous mutants derived from strain SC5314. A15 were obtained by selection with 0.5 μg/ml ANF (paternal strain SC5314), and A15-10 was selected using 8 μg/ml ANF (A15 paternal strain).

  • h WT, wild type.