Table 1. Sequence Polymorphisms and Susceptibility to POA and PZA of POA-Resistant M. tuberculosis Strains Subjected to Whole Genome Sequencing.
| mutations |
|||||
|---|---|---|---|---|---|
| M. tuberculosis H37Rv strain | panDa | clpC1a | other genes | POA broth MIC50b (mM) | PZA susceptibility result (S/R)c |
| H37Rv parent | 1.5 | S | |||
| POA B8 | G341A/Arg114Gln | 5.5 | R | ||
| POA B9 | A389G/Glu130Gly | Rv0980c (PE-PGRS 18): C129A/His43Gln | 6.0 | R | |
| Rv0980c (PE-PGRS 18): G217C/Glu73Gln | |||||
| Rv0980c (PE-PGRS 18): A1088C/Asn363Thr | |||||
| Rv2615c (PE-PGRS 45): G247A/Gly83Ser | |||||
| POA B10 | Δ418T | Rv1230c: T1078G/Cys360Gly | 6.0 | R | |
| POA B13 | T1024G/Phe342Val | ppsA: Ins2101C | 6.5 | R | |
| Rv1230c: T1078G/Cys360Gly | |||||
| trpA: A104G/Tyr35Cys | |||||
| cycA: A1297G/Thr433Ala | |||||
| secA2: G487T/Val163Leu | |||||
| POA B17 | G351T/Met117Ile | Rv0007: G451A/Ala151Thr | 6.0 | R | |
| Rv3645: G502C/Ala168Pro | |||||
| POA B20 | A1106G/His369Arg | Rv2061c: C39G/Tyr13* | 6.0 | R | |
| Rv2402: C1135A/Arg379Ser | |||||
| POA B21 | G296A/Gly99Asp | 6.0 | R | ||
| POA B26 | T49C/Cys17Arg | ltp1: C361A/Pro121Thr | 5.5 | R | |
| Rv3784: G965A/Gly322Asp | |||||
| POA K29 | A50G/Gln17Arg | pitA: Ins908G | 6.0 | R | |
| embA: A2695G/Thr899Ala | |||||
| POAR 1 [panD1]d | Δ380A | 6.0 | R | ||
| POAR 18 [clpC1-7]e | A625G/Lys209Glu | 6.0 | R | ||
a
Polymorphisms were identified by whole genome sequencing and verified by targeted sequencing as described in the text.
b
MIC50, POA concentration that inhibits 50% of growth compared to drug free control. Drug susceptibility tests were carried out three times independently, and mean values are shown.
c
BACTEC MGIT 960 test for susceptibility (S) or resistance (R) to 100 μg/mL PZA.
d
POAR 1 [panD1] was selected in vitro as described in ref (9).
e
POAR 18 [clpC1-7] was selected in vitro as described in ref (10).