TABLE 2.
ddn, fgd1, fbiA, fbiB, and fbiC mutations detected in MTBc strains resistant to DLMg
| Gene locus | Genomic coordinate(s)a | Mutation(s) (amino acid and nucleotide change)h | DLM MIC (μg/ml) | Countryb | Lineage (Coll lineage no.) | Treatment historyc | DR patternd | Frequencye | Eris ΔΔG (kcal/mol)f |
|---|---|---|---|---|---|---|---|---|---|
| ddn | 3986846 | M1fs (Del_2 t) | 2 | BGD | Eur-Amer. (4,1,2) | New | RIF, INH S | 1 | NA |
| ddn | 3986848 | P2Q (ccg/cAg) | 0.25 | AZE | Mainly T (4,8) | New | RIF, INH S | 1 | NA |
| ddn | 3986885 | S14fs (Del_41 g) | >4 | BGD | Beijing (2,2,1) | Retreatment | MDR | 1 | NA |
| ddn-fbiA | 3986923, 3640445i | W27Stop (tgg/tAg), prom (g-18a)i | >4 | BGD | EAI (1,1,3) | Retreatment | MDR | 1 | NA, NAi |
| ddn | 3986932 | R30H (cgc/cAc) | 1 | BGD | EAI (1,1,3) | Retreatment | RIF, INH S | 1 | NA |
| ddn | 3986944 | G34E (ggg/gAg) | 0.12 | AZE | LAM (4,3,3) | New | RIF, INH S | 9 | NA |
| ddn | 3987015 | Q58Stop (cag/Tag) | >4 | UKR | Beijing (2,2,1) | Retreatment | MDR, FQ R | 3 | NA |
| ddn-fbiA | 3987025, 3641164i | V61G (gtc/gGc), I208V (atc/Gtc)i | 0.12 | SA | Eur-Amer. (4,1,2) | New | RIF, INH S | 3 | 5.33, NAi |
| ddn-fbiA | 3987115, 3640714i | N91T (aac/aCc), V58I (gtc/Atc)i | 0.25 | AZE | Mainly T (4,8) | New | RIF, INH S | 3 | 8.45, NAi |
| ddn | 3987262 | T140I (acc/aTc) | 0.5 | BGD | S type (4,4,1,1) | New | RIF, INH S | 1 | 1.35 |
| fgd1 | 491723 | G314E (gga/gAa) | 0.12 | BGD | Beijing (2,2,1) | New | RIF, INH S | 1 | 0.6 |
| fbiA | 3640546 | K2E (aag/Gag) | 0.12 | AZE | Beijing (2,2,1) | Retreatment | RIF, INH S | 2 | NA |
| fbiA | 3641002 | V154I (gta/Ata) | 0.12 | BGD | Beijing (2,2,1) | Retreatment | MDR, FQ R | 1 | NA |
| fbiA-fbiB | 3641018, 3642877i | P159Q (ccg/cAg), K448R (aag/aGg)i | 0.12 | BGD | Delhi-CAS (3) | Retreatment | RIF, INH S | 1 | NA, NAi |
| fbiA | 3641164 | I208V (atc/Gtc) | 0.25 | BGD | Eur-Amer. (4,1,2) | New | RIF, INH S | 22 | NA |
| fbiA | 3641167 | I209V (atc/Gtc) | 0.5 | BGD | Eur-Amer. (4,5) | New | RIF, INH S | 1 | NA |
| fbiA | 3641403 | C287Stop (tgc/tgA) | 4 | PAK | EAI (1,1,2) | New | RIF, INH S | 1 | NA |
| fbiA | 3641453 | R304Q (cgg/cAg) | 0.25 | PAK | Delhi-CAS (3) | New | MDR | 1 | NA |
| fbiB | 3642195 | G221S (ggc/Agc) | 0.12 | BGD | Beijing (2,2,2) | New | FQ R | 4 | NA |
| fbiB | 3642204 | D224N (gac/Aac) | 0.5 | BGD | Delhi-CAS (3) | New | RIF, INH S | 2 | NA |
| fbiB | 3642351 | G273R (ggc/Cgc) | 0.25 | BGD | X type (4,1,1,3) | New | RIF, INH S | 1 | NA |
| fbiC | 1303241 | Y104C (tat/tGt) | 0.5 | AZE | Beijing (2,2,1) | Retreatment | RIF, INH S | 1 | NA |
| fbiC | 1303265 | G112A (ggc/gCc) | 0.12 | BGD | EAI (1,1,3) | New | RIF, INH S | 2 | NA |
| fbiC | 1303612 | L228F (ctc/Ttc) | 0.12 | BGD | EAI (1,1,3) | New | RIF, INH S | 1 | NA |
| fbiC-fbiB | 1303769, 3642223i | S280L (tcg/tTg), R230Q (cgg/cAg)i | 0.12 | BGD | EAI (1,1,3) | New | RIF, INH S | 1 | NA, NAi |
| fbiC | 1304498 | P523L (cct/cTt) | 0.5 | BGD | EAI (1,1,3) | New | RIF, INH S | 2 | NA |
| fbiC | 1305101 | N724S (aac/aGc) | 0.25 | BGD | Beijing (2,2,1) | New | RIF, INH S | 1 | NA |
| fbiC | 1305215 | S762N (agc/aAc) | 0.12 | BGD | Delhi-CAS (3) | Retreatment | FQ R | 1 | NA |
| fbiC | 1305434 | A835V (gcg/gTg) | 0.5 | BGD | EAI (1,1,3) | New | INH R | 17 | NA |
| fbiC | 1305494 | A855fs (Del 62 nt) | 0.5 | SA | Haarlem (4,1,2,1) | New | RIF, INH S | 28 | NA |
| fbiC-fbiB | 1305494, 3642874i | A855fs (Del 62 nt), L447R (ctg/cGg)i | 0.25 | SA | Mainly T (4,8) | Retreatment | MDR | 1 | NA, NAi |
| fbiC | 1305496 | A856P (gcc/Ccc) | 0.25 | BGD | EAI (1,1,3) | New | RIF, INH S | 1 | NA |
Genomic position in reference to the H37Rv genome (GenBank accession number NC_000962.3).
Country of MTBc isolate origin: Pakistan (PAK), Bangladesh (BGD), Ukraine (UKR), Azerbaijan (AZE), or South Africa (SA).
Patient treatment history: “New,” new TB case; “Retreatment,” patient with previous TB history and treatment.
Drug resistance pattern of the isolates (see Data Set S1 in the supplemental material).
Frequency of mutation in the WHO database.
ΔΔG values calculated using Eris software are reported where applicable (Data Set 2).
All the information is reported for each DLM resistance-related mutation (MIC ≥ 0.12) and for the MTBc isolates tested for DLM susceptibility. prom, promoter; Eur-Amer., Euro-American lineage.
Where the original codon and the mutated codon are separated by a slash in parentheses, the uppercase letter in the mutated codon represents the changed nucleotide.
There is a one-to-one correspondence between the pair of entries separated by a comma in the “Genomic coordinate(s)” column, the pair in the “Mutation(s)” column, and the pair in the “Eris ΔΔG” column.