Table 1. Singe nucleotide polymorphisms within the katG codon Ser315 in populations of isoniazid-resistant Mycobacterium tuberculosis H37Rv.
katG codon Ser315 sequence (amino acid change) | Culture condition and time-point of sample (MGT from time zero) | |||||
---|---|---|---|---|---|---|
INH69.3 7MGTpyro | INH69.312 MGTpyro | INH69.3 12 MGTsanger | INH23.36 MGTpyro | INH23.313MGTpyro | INH23.313MGTsanger | |
AGC (WT) | 9 | 4 | 0 | 59 | 86 | 77 (65) |
AAC (S315N) | 33 | 33 | 27 | 0 | 2 | 2 |
AGA (S315R) | 3 | 6 | 5 | 0 | 6 | 7 |
ATC (S315I) | 19 | 20 | 29 | 1 | 1 | 1 |
AGG (S315R) | 0 | 0 | 0 | 0 | 1 | 1 |
ACC (S315T) | 19 | 28 | 37 | 0 | 1 | 1 |
Mixed | 14 | 8 | 0 | 0 | 1 | 0 |
Putative duplication/partial deletion | 11 | |||||
Total number | 97 | 99 | 100 | 60 | 98 | 100 |
The number of singe nucleotide polymorphisms within the katG codon Ser315 in populations of isoniazid-resistant Mycobacterium tuberculosis H37Rv colonies that were isolated from continuous cultures growing either at a slow growth rate (Culture INH69.3) or fast growth rate (Culture INH23.3) that had been exposed to isoniazid. Colonies were selected on agar containing 2 x MIC isoniazid (1 mg L-1). One hundred colonies were picked after 6-7MGT and 12–13 MGT and were pyrosequenced at the katG codon Ser315. The total number of colonies, at each time-point, for which sequence information was obtained, is shown here. Colonies picked from Culture INH69.3 and Culture INH23.3 at 12 MGT or 13 MGT, respectively, were also subjected to Sanger sequencing and 65 (shown in bold; further detail in B) out of the 77 colonies that were found to be WT for the katG codon Ser315 were mutated elsewhere in the katG gene. Further detail on these mutations can be found in Table 2. Eleven colonies were found to have a putative duplication and partial deletion within katG in the fast growth culture, INH23.3, and the sequence data could not be fully interpreted.