Mycobacterium tuberculosis katG mutations conferring resistance to isoniazid

Accession ARO:3003392
CARD Short NameMtub_katG_INH
DefinitionkatG 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 Familyisoniazid resistant katG
Drug Classisoniazid-like antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsMycobacterium tuberculosisg+wgs
Classification9 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ isoniazid resistant katG [AMR Gene Family]
+ confers_resistance_to_antibiotic isoniazid [Antibiotic]

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)


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).

Prevalence: protein variant model (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GI
Mycobacterium tuberculosis99.8%0%67.43%0%
Show Perfect Only

Detection Models

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


  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB

Published Variants:

PMID in progress (single): P365R

PMID in progress (TB): W191R I317V V469L

PMID: 23744165V68G W91R L101P M126I R128Q P131Q P131R D194Y A234G S315I S315N S315T E454STOP R463L
PMID: 20054829D63E R104L W107F W107R H108E H108Q N138S N138D Y229F M255Y M255C M255I T262R T275V T275P W300G S315T S315N S315R S315I S315G W321F W328G W328F Y337C A350S R418L R463L L587M G629S D735N
PMID: 20211896H97R G123E Q127E N133T M176T P232S G299S S315R S315T S383P D387H D419H M420T R489S D542H R632C
PMID: 26251830G32D V47E Y64S Y95C P131T A139P D142G A162V D194G A256T G269D T306P R385W D387G T394M Q439P F483L A541D N596S,Y597H M624V T667P
PMID: 8585728D63E H108Q T262R S315T I335T A350S R463L G629S A717P
PMID: 24184004Y98C Q127P G269R Q352E A379T E506STOP
PMID: 24626681A431V
PMID: 25093512S17T A93T
PMID: 24468786D36E
PMID: 26157154A110V
PMID: 26092854A139V G300W
PMID: 21330112H276M Q295H
PMID: 7798673P2S S17N G19D S140N Q224E A243S A550D
PMID: 14638486G279D
PMID: 18508939G285D
PMID: 16870753G316D
PMID: 19520719S457I
PMID: 10645439G593D
PMID: 28904673S303C S303L Y304STOP D311S D311N L427I L430V T435R L436G Q471Y Q471H L472I L472Q L472K V473F V473W V473Y V473G V473N V473S V473D V473I V473K V473R V473M
PMID: 31100498M126I,R496L
PMID: 30583053G33V G111S G125S L147P C20R,S315T S211G,S315T G279V,L436P A312P S315T,G466R S315T,V581G H417Q V431A,G490S Q461P N508D E607A N660D W91STOP P92S,S315T nt1384-1:A
PMID: 36635309R78P Q88P W90R A109T A122D G124S L132R W161C G169S G182R F183L D189N D189G T191G E233G M257V T271I A312E T326P R385P Y413C D419Y Q439H R484H N655D D675Y T677P


High ConfidenceT667P W191R S315N S315T S315R I317V
Minimal ConfidenceR463L
Indeterminate ConfidenceV469L

>gb|CCP44675.1|-|Mycobacterium tuberculosis katG mutations conferring resistance to isoniazid [Mycobacterium tuberculosis H37Rv]

>gb|AL123456.3|-|2153889-2156111|Mycobacterium tuberculosis katG mutations conferring resistance to isoniazid [Mycobacterium tuberculosis H37Rv]