Table 3.
Resistance of M. tuberculosis inhA promoter and coding sequence mutants against the cofactor-independent diazaborine AN12855.
| Strain | SNPsa | Liquid IC90 (fold shift versus WT)b | ||
|---|---|---|---|---|
| fabG1inhA promoter (nt) | InhA (Am Ac) | AN12855 | INHc | |
| H37Rv | — | — | 0.06 μM | 0.1 μM |
| LP-0532543-RM18 | — | S19W | 1× | 1× |
| LP-0532543-RM28 | — | I21M | 1× | 1× |
| LP-0532543-RM34 | — | I21V | 1× | 2× |
| LP-0532543-RM13 | — | F41L | 1× | 1× |
| LP-0532543-RM19 | — | I47L | 3× | 1× |
| LP-0532543-RM1 | — | S94A | 1× | 2× |
| LP-0532543-RM6 | — | M103T | 2× | 1× |
| LP-0532543-RM2 | — | D148E | 5× | 1× |
| LP-0532543-RM4 | — | M161L | 4× | 1× |
| LP-0571426-RM24 | — | I194T | 3× | 3× |
| LP-0532543-RM41 | — | R195G | 16× | 2× |
| LP-0532543-RM9 | — | I202F | 2× | 1× |
| LP-0532543-RM7 | — | G205A | 2× | 1× |
| LP-0532543-RM11 | — | G205S | 2× | 1× |
| LP-0532543-RM3 | — | A206E | 2× | 1× |
| LP-0532543-RM14 | — | G212D | 3× | 1× |
| LP-0532543-RM16 | — | I215S | 15× | 1× |
| LP-0532543-RM37 | — | L269R | 1× | 1× |
| LP-0532543-RM30 | c-15t | — | 5× | 5× |
| LP-0532543-RM314 | c-15t | I47M | 7× | 5× |
| LP-0532543-RM301 | c-15t | N159K | 8× | 3× |
| LP-0532543-RM311 | c-15t | M161V | 84× | 5× |
| LP-0532543-RM304 | c-15t | T162M | 26× | 4× |
| LP-0532543-RM318 | c-15t | M199L | 10× | 4× |
| LP-0532543-RM313 | c-15t | G205D | 13× | 2× |
| LP-0532543-RM320 | c-15t | G208D | 16× | 4× |
a
No change in sequence from WT H37Rv.
b
Liquid IC90 values WT results are presented as μM, whereas RM IC90 are presented as the fold change compared with WT.
c
INH values are from McNeil et al (2017).