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. 2021 Sep 21;12(1):2415–2429. doi: 10.1080/21505594.2021.1959808

Table 2.

nsSNVs and larger deletions in 29 isolates from 11 serial samples obtained over 4.5 years from a chronically infected patient. Shown are the locus tags of the homologous genes in the reference strain ATCC 19977, the locus tags in the completed genome from the first sample (09–13-3), gene names, annotations, functional COG categories and names of the isolates exhibiting the mutations when compared to the initial isolate 09–13-3. Known associations to virulence and resistance of the genes or homologous genes in other mycobacterial species are indicated in the last two columns

Locus tag in ATCC 199771 Locus tag in
09–13-32 		Gene name3 Annotation3 Functional category4 Isolates exhibiting SNVs5 Association of gene to virulence Association of gene to resistance
MAB_0033c HIFIHNKG_00044 pknB Probable serine/threonine kinase PknB [K] [L] [T] 109–17-3 Survival in the host [25] ß-lactam, Rifampin [26]
MAB_0173 HIFIHNKG_00191   UbiA prenyltransferse family protein [H] 65–15-13   Ethambutol [27]
MAB_0186c HIFIHNKG_00204 embA Probable arabinosyltransferase A [M] 65–16-15   Ethambutol [27,28]
MAB_0189c HIFIHNKG_00207 embC Probable arabinosyltransferase C [M] 30–14-1, 40–14-3, 40–14-8, 58–15-2, 58–15-6, 58–15-9, 65–16-17, 65–16-20, 74–16-1, 74–16-2, 74–16-3, 74–16-4, 77–16-4, 79–16-1, 79–16-4, 79–16-6, 103–17-1 LAM biosynthesis [29] Ethambutol [29]
No homolog HIFIHNKG_00238   Hypothetical protein   58–15-4    
MAB_0277c HIFIHNKG_00346 tcyB Probable amino acid ABC transporter permease [E] [P] [T] 65–16-20    
MAB_0310c HIFIHNKG_00380   Putative cyclopropane-fatty-acyl-phospholipid synthase [M] 79–16-4 Survival in the host [30]  
MAB_0315 HIFIHNKG_00385 hsaA Flavin-dependent monooxygenase, oxygenase subunit HsaA [I] 40–14-1    
MAB_0415,MAB_0416c HIFIHNKG_00492,HIFIHNKG_00493 crp Putative Crp/Fnr-family transcriptional regulator, cAMP-binding protein [E] [G] [K] [T] 40–14-1, 74_16_2, 79–16-1, 79–16-4, 79–16-6   Clofazimine [31]
MAB_0673 HIFIHNKG_00715 tcrX Putative DNA-binding response regulator PhoP [K] [T] 65–16-15 Ironacquisition [32];
Virulence [33]		  
MAB_0816 HIFIHNKG_00859 betA Probable glucose-methanol-choline oxidoreductase [E] 74–16-2, 79–16-1, 79–16-4, 79–16-6    
MAB_0939 HIFIHNKG_00948 eryA Probable polyketide synthase, Malonyl CoA-acyl carrier proteintransacylase [Q] 40–14-3 Virulence [34,35] Amikacin, Cefoxitin, Imipenem, Linezolid [this study]
MAB_1080 HIFIHNKG_01092 mspD porin [S] 58–15-2, 103–17-3, 109–17-1 Ironacquisition [36];
Zinc acquisition [37];
Intracellular survival [38]		 Fluoroquinolone, Chloramphenicol [39];
Clarithromycin [40]
MAB_1129 HIFIHNKG_01124 tatD yabD Probable deoxyribonuclease [L] 58–15-9    
MAB_1156c HIFIHNKG_01160 lysA Diaminopimelate decarboxylase LysA [E] 77–16-4 Virulence [41]  
MAB_1499 HIFIHNKG_01502   Putative FAD dependent oxidoreductase [E] 74–16-3, 74–16-4    
MAB_1539c HIFIHNKG_01542   Mycobacterium membrane protein [S] 103–17-1    
MAB_1607 HIFIHNKG_01626 rnE Possible ribonuclease E [J] 103–17-3    
MAB_1678c HIFIHNKG_01697 furB Putative ferric uptake regulator FurB [P] 103–17-3, 109–17-1 Zn acquisition [42]  
MAB_1881c HIFIHNKG_01794   Putative transcriptional regulator, TetR family [K] 09–13-7, 23–13-1, 23–13-4, 30–14-1, 30–14-2, 40–14-1, 40–14-3, 40–14-8, 58–15-2, 58–15-4, 58–15-6, 58–15-9, 65–16-13, 65–16-15, 65–16-17, 65–16-20, 74–16-1, 74–16-2, 74–16-3, 74–16-4, 77–16-4, 77–16-7, 79–16-1, 79–16-4, 79–16-6, 103–17-1, 103–17-3, 109–17-1, 109–17-3   Clarithromycin [40]
MAB1991c HIFIHNKG_01937 mptA Integral membrane protein Alpha-(1-6- mannopyranosyltransferase A [S] 103–17-3, 109–17-1 LM/LAM synthesis [43]  
MAB_2161c HIFIHNKG_02096   Hypothetical low molecular weight antigen Mtb12 [S] 09–13-7    
MAB_2255 HIFIHNKG_02189   Probable non-ribosomal peptide synthetase [Q] 109–17-3    
MAB_2256 HIFIHNKG_02190   Probable polyketide synthase [Q] 103–17-3    
MAB_2299c HIFIHNKG_02233   Possible transcriptional regulatory protein [K] 79–16-4   Clofazimine, Bedaquiline [31,44]
MAB_2570c HIFIHNKG_02505 mmpL Probable membrane protein, MmpL family [D] 65–16-20, 77–16-4 Transport of cell wall lipids [45] Antibiotics [45]
MAB_2645c HIFIHNKG_02588 trpC Indole-3-glycerol-phosphate synthase [E] 74–16-3, 74–16-4 Survival in host cells [46]  
MAB_2679 HIFIHNKG_02622   Uncharacterized protein [S] 74–16-1    
MAB_2788 HIFIHNKG_02733 ggtB Gamma-glutamyl-transpeptidase [E] 77–16-4 Survival in host cells [47]  
MAB_2825 HIFIHNKG_02770   Acetyltransferase family protein [I] 103–17-3    
No homolog HIFIHNKG_02868   Hypothetical protein   40–14-1    
MAB_3029 HIFIHNKG_02972 ideR Iron-dependent repressor [K] 65–16-20, 77–16-4 Iron acquisition [48]  
MAB_3034 HIFIHNKG_02977   Alpha/beta hydrolase fold family hydrolase [I] 65–16-20, 77–16-4    
MAB_3036c HIFIHNKG_02979 nrdR Transcriptional repressor NrdR [K] 40–14-3    
MAB_3404c HIFIHNKG_03344 nrdF Ribonucleoside-diphosphate reductase subunit beta [F] 74–16-1, 103–17-1    
No homolog HIFIHNKG_03363   Hypothetical protein [S] 74–16-3    
No homolog HIFIHNKG_03364   Hypothetical protein [S] 74–16-3, 74–16-4    
MAB_3623 HIFIHNKG_03588   Probable transcriptional regulatory protein, AraC family [K] 65–16-20    
No homolog HIFIHNKG_03589   Hypothetical Gtr-like protein [I] [M] [S] 77–16-7, 109–17-3    
MAB_3669 HIFIHNKG_03634   Uncharacterized protein [S] 40–14-8    
MAB_3698 HIFIHNKG_03662   Putative ABC transporter [T] [V] 40–14-3, 40–14-8, 58–15-2, 74–16-2, 79–16-1, 79–16-4, 79–16-6    
MAB_3719c HIFIHNKG_03684 choD Putative cholesterol oxidase ChoD [E] 103–17-3, 109–17-1 Survival in host cells [49]  
MAB_4098c HIFIHNKG_04080 mps2, lgrD_2 Probable peptide synthetase NRP [Q] 58–15-4, 103–17-3, 109–17-1 Virulence [35,50] Amikacin, Cefoxitin, Imipenem, Linezolid [this study]
MAB_4099c HIFIHKG_04081 mps1, lgrC_1 Probable non-ribosomal peptide synthetase [Q] 58–15-2, 65–16-17, 65–16-20, 74–16-3, 74–16-4, 79–16-1 Virulence [35,50] Amikacin, Cefoxitin, Imipenem, Linezolid [this study]; Clofazimine [31]
MAB_4103c HIFIHNKG_04086   Probable methyltransferase [Q] 74–16-3, 74–16-4 Virulence [51]  
MAB_4105c HIFIHNKG_04088 mtfD Methyltransferase [E] [S] 74–16-3, 74–16-4    
MAB_4320c HIFIHNKG_04305   Putative TetR transcriptional regulator [K] 103–17-3    
MAB_4372 HIFIHNKG_04358   Putative 3-(2,3-dihydroxyphenyl) propionic acid dioxygenase [S] 58–15-2    
MAB_4654 HIFIHNKG_04625 mauC Conserved hypothetical protein (plastocyanin-like) [C] 74–16-3, 74–16-4    
MAB_4690c HFIHNKG_04663 lgrC_2 Probable non-ribosomal peptide synthetase PstA, Linear gramicidin synthase subunit C [Q] 65–16-17    
MAB_4695c HIFIHNKG_04668   Putative glycosyltransferase/rhamnosyltransferase [C] [G] 65–16-20    
MAB_4760 HIFIHNKG_04733 nox Probable nitroreductase [C] 109–17-3    
MAB_r5052   rrl 23S rRNA   103–17-3, 109–17-1   Clarithromycin [52]

1accession: NC010397.1; 2 accession: ERS4791737; 3 according to NCBI (https://www.ncbi.nlm.nih.gov/), STRING (https://string-db.org/), Uniprot (https://www.uniprot.org/); 4 according to EggNOG (http://eggnog5.embl.de/#/app/seqscan). 5 See Supplementary Table S3 for details of isolates. 4 COG categories are: [C] Energy production and conversion, [D] Cell cycle control, cell division, chromosome partitioning, [E] Amino acid transport and metabolism, [F] Nucleotide transport and metabolism, [G] Carbohydrate transport and metabolism, [H] Coenzyme transport and metabolism, [I] Lipid transport and metabolism, [J] Translation, ribosomal structure and biogenesis, [K] Transcription, [L] Replication, recombination and repair, [M] Cell wall/membrane/envelope biogenesis, [P] Inorganic ion transport and metabolism, [Q] Secondary metabolites biosynthesis, transport and catabolism, [S] Function unknown, [T] Signal transduction mechanisms, [V] Defense mechanisms. nsSNV: non-synonymous small nucleotide variation.