| Accession | ARO:3003392 |
| Synonym(s) | Rv1908c |
| CARD Short Name | Mtub_katG_INH |
| Definition | katG is a catalase-peroxidase that catalyzes the activation of isoniazid. Isoniazid inhibits mycolic acid synthesis, which prevents cell wall synthesis in mycobacteria. Mutations in katG results in inability to activate isoniazid. Over 280 different mutations have been documented in PubMed for katG, with mutations to Ser315 being the most prevalent. |
| AMR Gene Family | isoniazid resistant katG |
| Drug Class | isoniazid-like antibiotic |
| Resistance Mechanism | antibiotic target alteration |
| Resistomes with Sequence Variants | Mycobacterium tuberculosisg+wgs |
| Classification | 9 ontology terms | Show + process or component of antibiotic biology or chemistry + mechanism of antibiotic resistance + antibiotic target alteration [Resistance Mechanism] + mutation conferring antibiotic resistance + determinant of antibiotic resistance + antibiotic molecule + antibiotic resistant gene variant or mutant + isoniazid-like antibiotic [Drug Class] + antibiotic resistant katG |
| Parent Term(s) | 2 ontology terms | Show + confers_resistance_to_antibiotic isoniazid [Antibiotic] + isoniazid resistant katG [AMR Gene Family] |
| Publications | Jagielski T, et al. 2013. Pneumonol Alergol Pol 81(4): 298-307. Identification and analysis of mutations in the katG gene in multidrug-resistant Mycobacterium tuberculosis clinical isolates. (PMID 23744165) Khadka JB, et al. 2011. Nepal Med Coll J 13(3): 147-151. Study of rifampicin and isoniazid resistance mutation genes of M. tuberculosis isolates in Nepal. (PMID 22808802) Cade CE, et al. 2010. Protein Sci. 19(3):458-74 Isoniazid-resistance conferring mutations in Mycobacterium tuberculosis KatG: catalase, peroxidase, and INH-NADH adduct formation activities. (PMID 20054829) Ando H, et al. 2010. Antimicrob. Agents Chemother. 54(5):1793-9 Identification of katG mutations associated with high-level isoniazid resistance in Mycobacterium tuberculosis. (PMID 20211896) Torres JN, et al. 2015. Emerg Microbes Infect 4(7):e42 Novel katG mutations causing isoniazid resistance in clinical M. tuberculosis isolates. (PMID 26251830) Rouse DA, et al. 1995. Antimicrob. Agents Chemother. 39(11):2472-7 Characterization of the katG and inhA genes of isoniazid-resistant clinical isolates of Mycobacterium tuberculosis. (PMID 8585728) Tseng ST, et al. 2015. J Microbiol Immunol Infect 48(3):249-55 The mutations of katG and inhA genes of isoniazid-resistant Mycobacterium tuberculosis isolates in Taiwan. (PMID 24184004) Lu J, et al. 2014. Mol Med Rep 9(5):2031-5 Analysis of mutational characteristics of the drug-resistant gene katG in multi-drug resistant Mycobacterium tuberculosis L-form among patients with pneumoconiosis complicated with tuberculosis. (PMID 24626681) de Freitas FA, et al. 2014. PLoS ONE 9(8):e104100 Multidrug resistant Mycobacterium tuberculosis: a retrospective katG and rpoB mutation profile analysis in isolates from a reference center in Brazil. (PMID 25093512) Loots du T, et al. 2014. Antimicrob. Agents Chemother. 58(4):2144-9 An altered Mycobacterium tuberculosis metabolome induced by katG mutations resulting in isoniazid resistance. (PMID 24468786) Brossier F, et al. 2015. J. Clin. Microbiol. 53(9):3104 Characterization of a Clone of Mycobacterium tuberculosis Clinical Isolates with Mutations in KatG (A110V), EthA (Q269STOP), and the inhA Promoter (-15C→T). (PMID 26157154) Salvatore PP, et al. 2016. J. Infect. Dis. 213(1):149-55 Fitness Costs of Drug Resistance Mutations in Multidrug-Resistant Mycobacterium tuberculosis: A Household-Based Case-Control Study. (PMID 26092854) Ramasubban G, et al. 2011. Int. J. Antimicrob. Agents 37(4):368-72 Detection of novel coupled mutations in the katG gene (His276Met, Gln295His and Ser315Thr) in a multidrug-resistant Mycobacterium tuberculosis strain from Chennai, India, and insight into the molecular mechanism of isoniazid resistance using structural bioinformatics approaches. (PMID 21330112) Cockerill FR, et al. 1995. J. Infect. Dis. 171(1):240-5 Rapid identification of a point mutation of the Mycobacterium tuberculosis catalase-peroxidase (katG) gene associated with isoniazid resistance. (PMID 7798673) Morlock GP, et al. 2003. Antimicrob Agents Chemother 47(12): 3799-3805. ethA, inhA, and katG loci of ethionamide-resistant clinical Mycobacterium tuberculosis isolates. (PMID 14638486) Abe C, et al. 2008. J. Clin. Microbiol. 46(7):2263-8 Biological and molecular characteristics of Mycobacterium tuberculosis clinical isolates with low-level resistance to isoniazid in Japan. (PMID 18508939) Hazbón MH, et al. 2006. Antimicrob. Agents Chemother. 50(8):2640-9 Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis. (PMID 16870753) Bolotin S, et al. 2009. J. Antimicrob. Chemother. 64(2):263-6 Molecular characterization of drug-resistant Mycobacterium tuberculosis isolates from Ontario, Canada. (PMID 19520719) Ramaswamy S, et al. 1998. Tuber. Lung Dis. 79(1):3-29 Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. (PMID 10645439) Takawira FT, et al. 2017. Pan Afr Med J 27:145 Mutations in rpoB and katG genes of multidrug resistant mycobacterium tuberculosis undetectable using genotyping diagnostic methods. (PMID 28904673) Bouziane F, et al. 2019. J Glob Antimicrob Resist : First genetic characterization of multi-drug resistant Mycobacterium tuberculosis isolates from Algeria. (PMID 31100498) Islam MM, et al. 2019. Clin. Microbiol. Infect. 25(8):1041.e1-1041.e7 Detection of novel mutations associated with independent resistance and cross-resistance to isoniazid and prothionamide in Mycobacterium tuberculosis clinical isolates. (PMID 30583053) Thwe EP, et al. 2021. World J Microbiol Biotechnol 37(11):194 Novel mutations detected from drug resistant Mycobacterium tuberculosis isolated from North East of Thailand. (PMID 34642828) Napier G, et al. 2023. Sci Rep 13(1):623 Large-scale genomic analysis of Mycobacterium tuberculosis reveals extent of target and compensatory mutations linked to multi-drug resistant tuberculosis. (PMID 36635309) Ezewudo M, et al. 2018. Sci Rep 8(1):15382 Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase. (PMID 30337678) |
Prevalence of Mycobacterium tuberculosis katG mutations conferring resistance to isoniazid among the sequenced genomes, plasmids, and whole-genome shotgun assemblies available at NCBI or IslandViewer for 413 important pathogens (see methodological details and complete list of analyzed pathogens). Values reflect percentage of genomes, plasmids, genome islands, or whole-genome shotgun assemblies that have at least one hit to the AMR detection model. Default view includes percentages calculated based on Perfect plus Strict RGI hits. Select the checkbox to view percentages based on only Perfect matches to AMR reference sequences curated in CARD (note: this excludes resistance via mutation as references in protein variant models are often wild-type, sensitive sequences).
| Species | NCBI Chromosome | NCBI Plasmid | NCBI WGS | NCBI GI |
|---|---|---|---|---|
| Mycobacterium tuberculosis | 99.8% | 0% | 67.43% | 0% |
Model Type: protein variant model
Model Definition: Protein Variant Models (PVM) perform a similar search as Protein Homolog Models (PHM), i.e. detect protein sequences based on their similarity to a curated reference sequence, but secondarily screen query sequences for curated sets of mutations to differentiate them from antibiotic susceptible wild-type alleles. PVMs are designed to detect AMR acquired via mutation of house-keeping genes or antibiotic targets, e.g. a mutated gyrase resistant to aminocoumarin antibiotics. PVMs include a protein reference sequence (often from antibiotic susceptible wild-type alleles), a curated bit-score cut-off, and mapped resistance variants. Mapped resistance variants may include any or all of single point mutations, insertions, or deletions curated from the scientific literature. A Strict RGI match has a BLASTP bit-score above the curated BLASTP cutoff value and contains at least one curated mutation from amongst the mapped resistance variants, while a Loose RGI match has a bit-score less than the curated BLASTP bit-score cut-off but still contains at least one curated mutation from amongst the mapped resistance variants.
Bit-score Cut-off (blastP): 1400
Legend:
Published Variants:
| PMID: 23744165 | V68G W91R L101P M126I R128Q P131R P131Q D194Y S315T S315N S315I E454STOP R463L +nt135:T |
| PMID: 20054829 | D63E R104L W107R W107F H108E H108Q N138D N138S Y229F M255C M255I M255Y T262R T275P T275V W300G S315G S315R S315I S315N S315T W321F W328G W328F Y337C A350S R418L R463L L587M G629S D735N |
| PMID: 20211896 | H97R G123E Q127E N133T M176T P232S G299S S315T S315R S383P D387H D419H M420T R489S D542H R632C -nt571:GGCGGC |
| PMID: 26251830 | G32D V47E Y64S Y95C P131T A139P D142G A162V D194G A256T G269D T306P R385W D387G T394M Q439P F483L A541D N596S,Y597H M624V T667P |
| PMID: 8585728 | D63E H108Q T262R S315T I335T A350S R463L G629S |
| PMID: 24184004 | Q127P Q352E E506STOP Y98C G269R A379T +nt518:GGTC |
| PMID: 25093512 | S17T A93T -nt126:G -nt1293:G -nt1501:G -nt1525:A -nt241:G -nt249:G +nt325:T -nt368:G +nt392:T -nt54:C -nt60:A -nt81:C |
| PMID: 26157154 | A110V |
| PMID: 26092854 | A139V |
| PMID: 21330112 | H276M Q295H |
| PMID: 7798673 | P2S S17N G19D S140N Q224E A243S A550D |
| PMID: 14638486 | G279D |
| PMID: 18508939 | G285D |
| PMID: 16870753 | G316D |
| PMID: 19520719 | S457I |
| PMID: 10645439 | G593D |
| PMID: 28904673 | S303L S303C Y304STOP D311N D311S L427I L430V T435R L436G Q471Y Q471H L472K L472Q L472I V473D V473I V473K V473R V473S V473M V473N V473F V473W V473Y V473G |
| PMID: 31100498 | M126I,R496L |
| PMID: 30583053 | G33V G111S G125S L147P C20R,S315T S211G,S315T G279V,L436P A312P S315T,G466R S315T,V581G H417Q V431A,G490S Q461P N508D E607A N660D W91STOP P92S,S315T -nt1384:A |
| PMID: 34642828 | P365R |
| PMID: 36635309 | R78P Q88P W90R A109T A122D G124S L132R W161C G169S G182R F183L D189N D189G E233G M257V T271I A312E T326P R385P Y413C D419Y Q439H R484H N655D D675Y T677P |
| PMID: 30337678 | W191R S315N S315R S315T I317V R463L V469L T667P |
ReSeqTB:
| High Confidence | T667P W191R S315N S315T S315R I317V |
| Minimal Confidence | R463L |
| Indeterminate Confidence | V469L |