TABLE 5.
Frequencies of mutations in 12 strains by single-step selection
| Straina | Selecting drugb | Frequency of mutation at:
|
|||
|---|---|---|---|---|---|
| MIC | 2× MIC | 4× MIC | 8× MIC | ||
| 1 | ERY | 1.1 × 10−4 | 4.0 × 10−8 | <1.0 × 10−9 | <1.0 × 10−9 |
| AZI | 3.3 × 10−4 | <1.7 × 10−10 | <1.7 × 10−10 | <1.7 × 10−10 | |
| CLARI | 2.5 × 10−7 | 5.0 × 10−8 | <5.0 × 10−10 | <5.0 × 10−10 | |
| TELI | 2.5 × 10−8 | 5.0 × 10−10 | 5.0 × 10−10 | <5.0 × 10−10 | |
| CLINDAb | 2.0 × 10−8 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | |
| GW 708 | 1.3 × 10−8 | <1.3 × 10−9 | <1.3 × 10−9 | <1.3 × 10−9 | |
| GW 773 | 1.0 × 10−7 | 6.7 × 10−10 | <3.3 × 10−10 | <3.3 × 10−10 | |
| 2 | ERY | 1.2 × 10−3 | <2.0 × 10−8 | <2.0 × 10−8 | <2.0 × 10−8 |
| AZI | 6.7 × 10−9 | <1.1 × 10−9 | <1.1 × 10−9 | <1.1 × 10−9 | |
| CLARI | 2.5 × 10−4 | 1.5 × 10−9 | 1.5 × 10−9 | <5.0 × 10−10 | |
| TELI | 2.0 × 10−7 | 4.0 × 10−9 | <1.0 × 10−9 | <1.0 × 10−9 | |
| CLINDA | <7.1 × 10−10 | <7.1 × 10−10 | <7.1 × 10−10 | <7.1 × 10−10 | |
| GW 708 | 1.0 × 10−7 | <2.0 × 10−9 | <2.0 × 10−9 | <2.0 × 10−9 | |
| GW 773 | 1.5 × 10−7 | <2.5 × 10−9 | <2.5 × 10−9 | <2.5 × 10−9 | |
| 3 | ERY | 9.2 × 10−6 | 5.7 × 10−9 | 1.4 × 10−9 | <1.4 × 10−9 |
| AZI | 2.0 × 10−8 | <1.0 × 10−9 | <1.0 × 10−9 | <1.0 × 10−9 | |
| CLARI | 1.5 × 10−6 | 2.5 × 10−8 | 1.0 × 10−9 | 1.5 × 10−9 | |
| TELI | 1.7 × 10−8 | 3.3 × 10−9 | 1.3 × 10−9 | <6.7 × 10−10 | |
| CLINDA | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | |
| GW 708 | 5.0 × 10−9 | <1.0 × 10−9 | <1.0 × 10−9 | <1.0 × 10−9 | |
| GW 773 | 7.5 × 10−8 | 7.5 × 10−9 | <2.5 × 10−10 | <2.5 × 10−10 | |
| 4 | ERY | 2.5 × 10−7 | <5.0 × 10−9 | <5.0 × 10−9 | <5.0 × 10−9 |
| AZI | 2.3 × 10−6 | <3.3 × 10−9 | <3.3 × 10−9 | <3.3 × 10−9 | |
| CLARI | 3.3 × 10−6 | 2.5 × 10−9 | <5.0 × 10−10 | <5.0 × 10−10 | |
| TELI | 5.0 × 10−8 | 5.0 × 10−9 | <5.0 × 10−10 | <5.0 × 10−10 | |
| CLINDA | 1.7 × 10−9 | <3.3 × 10−10 | <3.3 × 10−10 | <3.3 × 10−10 | |
| GW 708 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | |
| GW 773 | 2.5 × 10−9 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | |
| 5 | ERYc | 6.5 × 10−8 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 |
| AZI | 5.0 × 10−8 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | |
| CLARIc | 3.0 × 10−4 | 5.0 × 10−9 | <5.0 × 10−9 | <5.0 × 10−9 | |
| TELIc | 1.0 × 10−7 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | |
| CLINDA | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | |
| GW 708c | 2.5 × 10−9 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | |
| GW 773c | 3.5 × 10−7 | 3.5 × 10−8 | <5.0 × 10−10 | <5.0 × 10−10 | |
| 6 | ERY | 2.0 × 10−6 | <1.0 × 10−9 | <1.0 × 10−9 | <1.0 × 10−9 |
| AZI | 4.4 × 10−9 | <1.1 × 10−9 | <1.1 × 10−9 | <1.1 × 10−9 | |
| CLARI | 7.5 × 10−5 | 5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | |
| TELI | 1.5 × 10−8 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | |
| CLINDA | <2.5 × 10−10 | <2.5 × 10−10 | <2.5 × 10−10 | <2.5 × 10−10 | |
| GW 708 | 3.8 × 10−8 | <1.2 × 10−9 | <1.2 × 10−9 | <1.2 × 10−9 | |
| GW 773 | 1.0 × 10−7 | <3.3 × 10−10 | <3.3 × 10−10 | <3.3 × 10−10 | |
| 7 | ERY | 8.0 × 10−4 | 4.0 × 10−5 | 3.0 × 10−6 | 2.0 × 10−6 |
| AZI | 5.0 × 10−6 | 5.0 × 10−7 | 8.3 × 10−9 | <1.7 × 10−9 | |
| CLARI | 5.0 × 10−5 | 1.8 × 10−7 | 1.3 × 10−8 | 1.7 × 10−10 | |
| TELI | 2.5 × 10−6 | 3.8 × 10−9 | <2.5 × 10−10 | <2.5 × 10−10 | |
| CLINDA | 2.0 × 10−4 | 1.4 × 10−8 | <2.0 × 10−10 | <2.0 × 10−10 | |
| GW 708 | 3.0 × 10−5 | 2.0 × 10−7 | 2.0 × 10−8 | <1.0 × 10−9 | |
| GW 773 | 1.2 × 10−4 | 1.2 × 10−7 | 2.0 × 10−9 | <2.0 × 10−10 | |
| 8 | ERY | 1.0 × 10−3 | 1.4 × 10−5 | 2.0 × 10−7 | 2.0 × 10−8 |
| AZI | 2.0 × 10−4 | 1.0 × 10−6 | 1.0 × 10−7 | <5.0 × 10−9 | |
| CLARI | 2.7 × 10−4 | 5.4 × 10−7 | <9.1 × 10−10 | <9.1 × 10−10 | |
| TELI | 1.8 × 10−4 | 4.5 × 10−8 | <9.1 × 10−10 | <9.1 × 10−10 | |
| CLINDA | 1.5 × 10−4 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | |
| GW 708 | 1.0 × 10−3 | 1.5 × 10−6 | 1.0 × 10−8 | <5.0 × 10−10 | |
| GW 773 | >1.0 × 10−3 | 2.0 × 10−5 | 6.7 × 10−9 | 6.7 × 10−10 | |
| 9 | ERY | 2.0 × 10−2 | 4.0 × 10−3 | 2.0 × 10−4 | 2.0 × 10−5 |
| AZI | 1.2 × 10−3 | 2.0 × 10−5 | <1.0 × 10−8 | <1.0 × 10−8 | |
| CLARI | 2.0 × 10−3 | 6.0 × 10−4 | <1.0 × 10−9 | <1.0 × 10−9 | |
| TELI | 1.0 × 10−5 | 3.5 × 10−9 | <5.0 × 10−10 | <5.0 × 10−10 | |
| CLINDA | 3.0 × 10−3 | 1.5 × 10−3 | 1.0 × 10−7 | <1.0 × 10−9 | |
| GW 708 | 2.1 × 10−3 | 8.6 × 10−7 | 2.1 × 10−8 | <1.4 × 10−9 | |
| GW 773 | >4.3 × 10−3 | 4.3 × 10−6 | 5.7 × 10−9 | <1.4 × 10−9 | |
| 10 | ERY | NTd | NT | NT | NT |
| AZI | NT | NT | NT | NT | |
| CLARI | NT | NT | NT | NT | |
| TELI | >1.0 × 10−3 | >1.0 × 10−3 | >1.0 × 10−3 | >1.0 × 10−3 | |
| CLINDA | NT | NT | NT | NT | |
| GW 708 | >1.9 × 10−3 | >1.9 × 10−3 | >1.9 × 10−3 | >1.9 × 10−3 | |
| GW 773 | >1.9 × 10−3 | >1.9 × 10−3 | >1.9 × 10−3 | >1.9 × 10−3 | |
| 11 | ERY | NT | NT | NT | NT |
| AZI | NT | NT | NT | NT | |
| CLARI | NT | NT | NT | NT | |
| TELI | >4.3 × 10−4 | >4.3 × 10−4 | 4.3 × 10−8 | 5.7 × 10−9 | |
| CLINDA | NT | NT | NT | NT | |
| GW 708 | 4.0 × 10−5 | 1.0 × 10−6 | 1.0 × 10−6 | 2.5 × 10−7 | |
| GW 773 | >1.5 × 10−3 | >1.5 × 10−3 | >1.5 × 10−3 | >1.5 × 10−7 | |
| 12 | ERY | NT | NT | NT | NT |
| AZI | NT | NT | NT | NT | |
| CLARI | NT | NT | NT | NT | |
| TELI | 1.1 × 10−7 | 8.0 × 10−8 | <6.7 × 10−10 | <6.7 × 10−10 | |
| CLINDA | NT | NT | NT | NT | |
| GW 708 | 2.0 × 10−6 | 1.0 × 10−6 | 1.0 × 10−6 | 8.0 × 10−7 | |
| GW 773 | >1.5 × 10−3 | 7.5 × 10−4 | 3.0 × 10−4 | 1.0 × 10−4 | |
a
Strains 7 to 9 are mef(E) positive, and strains 10 to 12 are erm(B) positive.
b
See footnote a of Table 4 for the definition of the drug abbreviations.
c
Mutants selected from strains 5 and 1 in single steps were analyzed for alterations in the sequences of 23S rRNA and the L4 and L22 proteins.
d
NT, not tested.