TABLE 1.
Distribution of the embCAB mutations in 60 ETB-S and 71 ETB-R isolates of the MTBC
| Resistance phenotype (total no. of isolates) | Phylogenetic lineage | No. of isolates | Mutation(s) in the embCAB locusa |
||
|---|---|---|---|---|---|
| Marker(s) of phylogenetic lineages | Mutation(s) potentially associated with ETB resistanceb | Synonymous mutation (excluding marker of phylogenetic lineage) | |||
| Susceptible (60) | T | 3 | |||
| T1 | 2 | ||||
| Cameroon | 3 | ||||
| LAM | 7 | ||||
| Ural | 1 | ||||
| S | 1 | ||||
| Uganda | 3 | ||||
| S | 1 | embC g363t (L121L) | |||
| LAM | 1 | embB t2280c (N760N) | |||
| Beijing | 10 | embA c228t (C76C) | |||
| Beijing | 1 | embA c228t (C76C) | EmbC V987A | ||
| Haarlem | 14 | EmbC V981L | |||
| Ghana | 2 | EmbC V981L | |||
| T3 variant | 2 | EmbC V981L | |||
| T3 variant | 1 | EmbC V981L | embB g132t (T44T) | ||
| T2 | 1 | EmbC V981L | |||
| X | 1 | EmbC V981L, embB g2895a (P965P), embC c1035g (R345R) | |||
| Haarlem | 1 | EmbC V981L | EmbC A426T | ||
| Delhi/CAS | 2 | EmbC R738Q | |||
| Cameroon | 1 | EmbB M306Ic | |||
| West africanum 2 | 1 | EmbB E378A, EmbC T270I | |||
| M. bovis | 1 | EmbB N13S, EmbB E378A, embB c351t (V117V), EmbC | |||
| T270I, embC c3108t (T1036T) | |||||
| Resistant (71) | Beijing | 3 | embA c228t (C76C) | EmbB M306V,c embCA -c12t | |
| LAM | 1 | EmbB M423T | EmbB M306V,c embCA -c16t | ||
| Beijing | 14 | embA c228t (C76C) | EmbB M306Vc | ||
| Beijing | 1 | embA c228t (C76C) | EmbB M306Vc | embB c1602t (D534D) | |
| LAM | 3 | EmbB M306Vc | |||
| T1 | 1 | EmbC V981L | EmbB M306Vc | ||
| S | 1 | EmbB M306Vc | |||
| Beijing | 5 | embA c228t (C76C) | EmbB M306Ic | ||
| Haarlem | 3 | EmbC V981L | EmbB M306Ic | ||
| T1 | 1 | EmbB M306Ic | |||
| T2 | 1 | EmbB M306Ic | embB g3081a (T1027T) | ||
| LAM | 5 | EmbB M306Ic | |||
| Ghana | 1 | EmbC V981L | EmbB M306I,c embCA -c11a | ||
| Beijing | 1 | embA c228t (C76C) | EmbB G406Cc | ||
| Beijing | 1 | embA c228t (C76C) | EmbB G406Sc | ||
| LAM | 1 | EmbB G406Ac | embB c2956t (L986L) | ||
| Haarlem | 1 | EmbC V981L | EmbB G406Ac | ||
| Beijing | 3 | embA c228t (C76C) | EmbB G406Dc | ||
| LAM | 1 | EmbB G406Dc | |||
| Beijing | 1 | embA c228t (C76C) | EmbB Q497Rc | ||
| Cameroon | 1 | EmbB Q497Rc | |||
| Ural | 1 | EmbB F330I | |||
| Beijing | 1 | embA c228t (C76C) | EmbB D354Ad | ||
| Ural | 1 | EmbB N399I | |||
| Beijing | 1 | embA c228t (C76C) | EmbB L402V | ||
| Ural | 1 | EmbB S426N | |||
| Beijing | 3e | embA c228t (C76C), embA a114g (Q38Q) | EmbB N296H | embA c1995t (H764H) | |
| X | 1 | EmbC V981L, embB g2895a (P965P) | embCA-c8a | ||
| Beijing | 1 | embA c228t (C76C) | embCA -c8t | ||
| Beijing | 1 | embA c228t (C76C) | embCA -c12t | ||
| LAM | 1 | embCA -c12t | |||
| Beijing | 1 | embA c228t (C76C) | embCA -c16t | ||
| Delhi/CAS | 1 | EmbC R738Q | embCA -c16t | ||
| Beijing | 1 | embA c228t (C76C) | embCA with deletion of cg at positions −21 and −20 | ||
| Beijing | 3e | embA c228t (C76C) | embCA -c12t, EmbB Y334H | ||
| Haarlem | 1 | EmbC V981L | embCA -c12t, EmbB D354Ad | embC t1677c (G559G) | |
| Uganda | 1 | EmbB A19D plus N296H, EmbA G5V | |||
| NEW-1 | 1 | ||||
a
Excluding the synonymous embC c2781t mutation (R927R) present in all ETB-S and ETB-R isolates.
b
embCA is the embC-embA intergenic region.
c
Implication in ETB resistance proven by site-directed mutagenesis or allelic exchange.
d
Involvement in ETB resistance suggested by the in vitro-selected mutant.
e
Isolates sharing identical MIRU codes and spoligotypes.