TABLE 1.
Impact of rifaximin resistance alleles on the fitness and growth of C. difficile
| Strain | MIC (μg/ml) | Substitution | Fitness (W)a | Doubling time (min) |
|---|---|---|---|---|
| CD43 (parent) | 0.125 | None | 1.00 | 97.3 ± 4.8 |
| CD43-D1 | >1,024 | Gln489Leu | 0.84 ± 0.05 | 89.4 ± 4.1 |
| CD43-D2 | >1,024 | Asp492Tyr | 0.80 ± 0.01 | 100.3 ± 9.2 |
| CD43-D3 | >1,024 | Asp492Tyr | 0.80 ± 0.08 | 118.2 ± 5.1 |
| CD43-D4 | >1,024 | Asp492Gly | 1.2 ± 0.12 | 92.3 ± 6.0 |
| CD43-A1 | >1,024 | His502Tyr | 1.20 ± 0.13 | NDb |
| CD43-A2 | >1,024 | His502Asn | 1.00 ± 0.13 | ND |
| CD43-D5 | >1,024 | Arg505Lys | 0.99 ± 0.008 | 95.3 ± 10.1 |
| CD43-D6 | >1,024 | Arg505Lys | ND | 110.0 ± 5.1 |
| CD43-D7 | >1,024 | Gly510Arg | 0.85 ± 0.12 | 90.3 ± 5.5 |
| CD43-D8 | >1,024 | Ser488Tyr | 0.85 ± 0.02 | ND |
| CD43-D9 | >1,024 | Ser550Tyr | 0.67 ± 0.05 | 104.2 ± 18.4 |
| CD43-D10 | >1,024 | Ser550Phe | 1.26 ± 0.13 | ND |
| CD1769 (parent) | 0.0625 | None | 1.00 | 97 ± 9.5 |
| CD1769-D1 | >1,024 | Asp492Tyr | ND | 98.9 ± 9.2 |
| CD1769-D2 | >1,024 | His502Arg | 0.91 ± 0.3 | 102.1 ± 10.7 |
| CD1769-D3 | >1,024 | Arg505Lys | 1.02 ± 0.15 | 102.0 ± 4.4 |
| CD1769-D4 | >1,024 | Ser507Leu | 0.57 ± 0.07 | 267.5 ± 37.1 |
| CD1769-D5 | >1,024 | Leu584Phe | 1.24 ± 0.07 | ND |
a
By convention, the fitness of the wild type is designated as 1. MICs were determined using two independent cultures in duplicates. A minimum of three independent replicates were performed to calculate W and doubling times.
b
ND, not determined.