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. 2020 Apr 21;6:100040. doi: 10.1016/j.tcsw.2020.100040

Table 3.

Whole genome sequencing results of M. bovis BCG spontaneous resistant mutants raised against HTB-03 and HTB-04. High frequency single nucleotide polymorphisms resulting in changes in the amino acid sequence are reported. Genomic positions of the SNP are relative to M. bovis BCG strain Pasteur 1173P2. The base changes (deletions, insertions or substitutions) are capitalized. The amino acid changes are documented, where *1, *2, *3 and *4 represent the generation of a stop codon, amino acid deletions, insertion of a base leading to an amino acid change and a subsequent frameshift, and amino acid insertions. Spontaneous resistant mutants are numbered and the MIC at which they were generated is shown. Dots represent areas where sequence coverage was not sufficient for analysis. Blank spaces indicate the absence of a base change relative to the reference strain.

Gene Genome position of SNP Codon change Amino acid changes Frequency of SNP HTB-03 Mutants
HTB-04 Mutants
50 × MIC
100 × MIC
20 × MIC
1 2 1 2 3 1 2 3
BCG_0220 244,283 taT/taG Y99*1 98.86 G
244,393 GTGGCGGCACAGgac/gac VAAQD137D*2 97.09 GTGGCGGCACAG GTGGCGGCACAG GTGGCGGCACAG GTGGCGGCACAG
244,500 Tct/Cct S172P 100 C
BCG_0404c 475,202 Gcc/Acc A143T 100 A A A A A A
Non-coding region 1,344,671 C/G 100 G G G G G G G G
1,344,672 G/C 100 C C C C C C C C
PE_PGRS28 1,661,298 Gcc/Acc A651T 100 . A . . . A . .
1,661,300 gTc/gGc V650G 100 . G . . . G . .
1,661,303 aTc/aAc I649N 100 . A . . . A . .
1,661,304 Atc/Gtc I649V 100 . G . . . G . .
1,661,306 aTc/aGc I648S 100 . G . . . G . .
1,661,307 Atc/Gtc I648V 100 . G . . . G . .
1,661,309 gAc/gGc D647G 100 . G . . . G . .
pks12 2,282,655 Ggt/Agt G2662S 100
2,282,656 tgG/tgA W2661*1 100
proB 2,702,724 Gcc/Tcc A232S 100 T
fadD28 3,237,397 ttt/ttAt F25L*3 100 TA TA TA TA TA TA
BCG_3499c 3,833,488 gcc/gcGGCc A433AA*4 100 GGC GGC GGC GGC GGC GGC GGC
cut3 3,854,969 ggc/gGTCgc G261GR*4 100 GTC GTC GTC GTC GTC GTC GTC
PE_PGRS53 3,907,860 Aac/Gac N599D 100 G G G G G G G G
PE_PGRS57 3,927,720 Acc/Gcc T598A 100 G . . . . G . .
BCG_3742 4,098,093 gaC/gaA D188E 100 A A A A A A
glpK 4,111,717 ttG/ttC L385F 100 C C C C C C