TABLE 4.
Cross-resistance of adamantyl urea and SQ109 spontaneous resistant mutants of M. tuberculosis H37Rv to AU1235, BM212, and SQ109
| Isolatea | MIC (μg/ml) forb: |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| WTc | AU2 | AU3 | AU4 | AU5 | AU6 | DA5_1 | DA5_2 | DA8_1 | DA8_2 | |
| AU1235 | 0.2–0.4 | >1.6 | >1.6 | >1.6 | >1.6 | >1.6 | >1.6 | 1.6 | >1.6 | 1.6 |
| BM212 | 1.25 | 10 | 5–10 | 10 | 5 | 5 | 10 | 10 | 10 | 5 |
| SQ109 | 1 | NDd | ND | ND | ND | ND | 4 | 2 | 2–8 | 2–4 |
The mutation for the isolates AU2, AU3, AU4, AU5, and AU6 is G253E, that for DA5_1 and DA5_2 is A700T, that for DA8_1 is L567P, and that for DA8_2 is Q40R. The adamantyl urea (isolates AU2, AU3, AU4, AU5, and AU6) and SQ109 (isolates DA5_1, DA5_2, DA8_1, and DA8_2) spontaneous resistant mutants of M. tuberculosis H37Rv were reported previously (9, 19).
The MICs, defined as the concentration of inhibitors that inhibited 100% of the growth and metabolic activity of the various M. tuberculosis H37Rv isolates, were determined in 96-well microtiter plates using the colorimetric resazurin assay in 7H9-OADC-Tween 80 broth at 37°C.
The wild-type (WT) strain was M. tuberculosis H37Rv TMC102.
ND, not determined.