Table 3.
Single nucleotide variants (non-synonymous and intergenic) identified as putative genomic markers of amoxicillin/clavulanate susceptibility.
| Genomic loci | Rv number | Gene name | Effect* | Amino acid effect | # Isolates | p-Value | LAM4 sub-clade |
|---|---|---|---|---|---|---|---|
| 664929 | Rv0571c-Rv0572c | – | C ➜ A | Intergenic | 28 | 1.28E − 04 | D |
| 761161 | Rv0667 | rpoB | cTg ➜ cCg | L452P | 36 | 2.40E − 04 | B |
| 1272321 | Rv1144-Rv1145 | − mmpL13a | C ➜ A | Intergenic | 36 | 2.40E − 04 | B |
| 2,300,674 | Rv2048c | pks12 | Aac ➜ Gac | N2105D | 36 | 2.40E − 04 | B |
| 2300676 | Rv2048c | pks12 | tAc ➜ tTc | Y2104F | 36 | 2.40E − 04 | B |
| 3889150 | Rv3471c | – | gaC ➜ gaA | D64E | 36 | 2.40E − 04 | B |
| 761110 | Rv0667 | rpoB | gAc ➜ gGc | D435G | 30 | 2.88E − 04 | C |
| 763123 | Rv0667 | rpoB | aTc ➜ aCc | I1106T | 30 | 2.88E − 04 | C |
| 2246032 | Rv2000 | – | cTg ➜ cCg | L275P | 30 | 2.88E − 04 | C |
| 4056430 | Rv3616c-Rv3617 | espA-ephA | T ➜ C | Intergenic | 30 | 2.88E − 04 | C |
| 1212626 | Rv1087 | PE_PGRS21 | gAc ➜ gCc | D356A | 36 | 3.04E − 04 | – |
| 7570 | Rv0006 | gyrA | gCg ➜ gTg | A90 V | 32 | 4.96E − 04 | – |
| 4269271 | Rv3806c | ubiA | gTg ➜ gCg | V188 A | 31 | 6.08E − 04 | – |
| 1532777 | Rv1361c | PPE19 | cAg ➜ cGg | Q286R | 45 | 1.10E − 03 | – |
| 122107 | Rv0103c | ctpB | Ggt ➜ Agt | G23S | 42 | 1.17E − 03 | A |
| 3272997 | Rv2936 | drrA | Agg ➜ Ggg | R262G | 42 | 1.17E − 03 | A |
| 283614 | Rv0236c | aftD | Agc ➜ Ggc | S1080G | 8 | 1.25E − 03 | – |
| 340372 | Rv0280 | PPE3 | Tcg ➜ Ccg | S337P | 8 | 1.25E − 03 | – |
| 2357269 | Rv2098c | PE_PGRS36 (pseudogene) | G➜ | Deletion | 8 | 1.25E − 03 | – |
| 3462135 | Rv3093c | – | tgC ➜ tgG | C210W | 8 | 1.25E − 03 | – |
| 3942640 | Rv3512 | PE_PGRS56 | aTt ➜ aCt | I306T | 8 | 1.25E − 03 | – |
| 2074509 | Rv1829-Rv1830 | – | C ➜ G | Intergenic | 45 | 1.40E − 03 | – |
Genomic loci as defined in the H37Rv reference genome. For single nucleotide polymorphisms ‘Effect’ indicates the base differences (base in reference ➜ alternative base), polymorphisms within coding sequence regions are shown as capital letters in the context of the codons to which they belong (other positions shown in lower case). # Isolates indicates the number of M. tuberculosis strains that contained the corresponding polymorphism. LAM4 sub-clade indicates the sub-clade for which the SNP in question is both unique to and conserved across the sub-clade. All SNVs having the same p-value represent the same evolutionary pattern. Of note, our analyses did not identify any associations between amoxicillin/clavulanate susceptibility and variation in genes previously implicated for this phenotype e.g. mycobacterial l,d-transpeptidases, carboxypeptidases, penicillin-binding proteins and the BlaC beta-lactamase among others (Dubée et al., 2012, Datta et al., 2006, Kumar et al., 2012, Flores et al., 2005, Bhakta and Basu, 2002, Danilchanka et al., 2008, Dinesh et al., 2013, Fukuda et al., 2013, McDonough et al., 2005) (Table S6).
Genomic loci as defined in the H37Rv reference genome. For single nucleotide polymorphisms ‘Effect’ indicates the base differences (base in reference ➜ alternative base), polymorphisms within coding sequence regions are shown as capital letters in the context of the codons to which they belong (other positions shown in lower case). # Isolates indicates the number of M. tuberculosis strains that contained the corresponding polymorphism. LAM4 sub-clade indicates the sub-clade for which the SNP in question is both unique to and conserved across the sub-clade. All SNVs having the same p-value represent the same evolutionary pattern. Of note, our analyses did not identify any associations between amoxicillin/clavulanate susceptibility and variation in genes previously implicated for this phenotype e.g. mycobacterial l,d-transpeptidases, carboxypeptidases, penicillin-binding proteins and the BlaC beta-lactamase among others (Dubée et al., 2012, Datta et al., 2006, Kumar et al., 2012, Flores et al., 2005, Bhakta and Basu, 2002, Danilchanka et al., 2008, Dinesh et al., 2013, Fukuda et al., 2013, McDonough et al., 2005) (Table S6).