TABLE 2.
Xenobiotic resistance of S. cerevisiae AD1-8u- strains overexpressing milbemycin α25-resistant Cdr1 mutants relative to AD/CDR1a
| Strainb | Fold-reduced resistance levels of: |
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Azolesc |
Other xenobioticsc |
||||||||||||
| FLC 306 | CLT 345 | VRC 349 | MCZ 416 | KTC 531 | PSC 701 | ITC 706 | CER 223 | CHX 281 | LaA 422 | R6G 479 | MON 681 | NIG 724 | |
| G521R | 4 | 4,096 | 8 | 16 | 64 | 512 | 128 | 2 | 2 | 64 | 8 | 256 | 512 |
| M639I | 1 | 1 | 1 | 4 | 2 | 16 | 2 | 2 | 2 | 1 | 2 | 1 | 1 |
| A713P | 2 | 8 | 2 | 8 | 8 | 32 | 32 | 2 | 2 | 4 | 1 | 1 | 16 |
| T1355N | 2 | 2 | 1 | 4 | 2 | 16 | 2 | 2 | 1 | 4 | 1 | 1 | 1 |
a
The maximum fold-reduced resistance levels (i.e., no transport) equaled the drug susceptibilities of the sensitive control strain AD/pABC3. They were 512 (FLC), 4,096 (CLT), 512 (VRC), 1,024 (MCZ), 1,024 (KTC), 2048 (PSC), 1,024 (ITC), 32 (CER), 128 (CHX), 512 (LaA), 64 (R6G), 4,096 (MON), and 2,048 (NIG), respectively (1 = no change).
b
G521R, AD/CDR1-G521R; M639I, AD/CDR1-M639I; A713P, AD/CDR1-A713P; T1355N, AD/CDR1-T1355N.
c
Cdr1 drug substrates are listed according to their molecular weight from lowest (left) to highest (right). Numbers underneath each compound are the molecular weights in Da.