Mycobacterium tuberculosis rpoB mutants conferring resistance to rifampicin

Accession ARO:3003283
CARD Short NameMtub_rpoB_RIF
DefinitionPoint mutations that occurs in Mycobacterium tuberculosis rpoB resulting in resistance to rifampicin.
AMR Gene Familyrifamycin-resistant beta-subunit of RNA polymerase (rpoB)
Drug Classrifamycin antibiotic
Resistance Mechanismantibiotic target alteration, antibiotic target replacement
Resistomes with Sequence VariantsMycobacterium tuberculosisg+wgs
Classification11 ontology terms | Show
Parent Term(s)5 ontology terms | Show
+ rifamycin-resistant beta-subunit of RNA polymerase (rpoB) [AMR Gene Family]
+ confers_resistance_to_antibiotic rifaximin [Antibiotic]
+ confers_resistance_to_antibiotic rifapentine [Antibiotic]
+ confers_resistance_to_antibiotic rifampin [Antibiotic]
+ confers_resistance_to_antibiotic rifabutin [Antibiotic]

Htike Min PK, et al. 2014. Southeast Asian J Trop Med Public Health 45(4): 843-852. Novel mutation detection IN rpoB OF rifampicin-resistant Mycobacterium tuberculosis using pyrosequencing. (PMID 25427352)

Campbell PJ, et al. 2011. Antimicrob Agents Chemother 55(5): 2032-2041. Molecular detection of mutations associated with first- and second-line drug resistance compared with conventional drug susceptibility testing of Mycobacterium tuberculosis. (PMID 21300839)

Madania A, et al. 2012. Pol J Microbiol 61(1): 23-32. Characterization of mutations causing rifampicin and isoniazid resistance of Mycobacterium tuberculosis in Syria. (PMID 22708343)

Mariam DH, et al. 2004. Antimicrob Agents Chemother 48(4): 1289-1294. Effect of rpoB mutations conferring rifampin resistance on fitness of Mycobacterium tuberculosis. (PMID 15047531)

Heep M, et al. 2001. J Clin Microbiol 39(1): 107-110. Frequency of rpoB mutations inside and outside the cluster I region in rifampin-resistant clinical Mycobacterium tuberculosis isolates. (PMID 11136757)

Heep M, et al. 2000. Antimicrob. Agents Chemother. 44(4):1075-7 Mutations in the beginning of the rpoB gene can induce resistance to rifamycins in both Helicobacter pylori and Mycobacterium tuberculosis. (PMID 10722516)

Taniguchi H, et al. 1996. FEMS Microbiol. Lett. 144(1):103-8 Rifampicin resistance and mutation of the rpoB gene in Mycobacterium tuberculosis. (PMID 8870258)

Cavusoglu C, et al. 2002. J. Clin. Microbiol. 40(12):4435-8 Characterization of rpoB mutations in rifampin-resistant clinical isolates of Mycobacterium tuberculosis from Turkey by DNA sequencing and line probe assay. (PMID 12454132)

Schilke K, et al. 1999. Int. J. Tuberc. Lung Dis. 3(7):620-6 Universal pattern of RpoB gene mutations among multidrug-resistant isolates of Mycobacterium tuberculosis complex from Africa. (PMID 10423225)

Sekiguchi J, et al. 2007. J Clin Microbiol 45(1): 179-192. Detection of multidrug resistance in Mycobacterium tuberculosis. (PMID 17108078)

Zenteno-Cuevas R, et al. 2009. Mem. Inst. Oswaldo Cruz 104(3):468-72 Mutations in rpoB and katG genes in Mycobacterium isolates from the Southeast of Mexico. (PMID 19547874)

Sajduda A, et al. 2004. J. Clin. Microbiol. 42(6):2425-31 Molecular characterization of rifampin- and isoniazid-resistant Mycobacterium tuberculosis strains isolated in Poland. (PMID 15184414)

Kapur V, et al. 1994. J. Clin. Microbiol. 32(4):1095-8 Characterization by automated DNA sequencing of mutations in the gene (rpoB) encoding the RNA polymerase beta subunit in rifampin-resistant Mycobacterium tuberculosis strains from New York City and Texas. (PMID 8027320)

Siddiqi N, et al. 2002. Antimicrob. Agents Chemother. 46(2):443-50 Molecular characterization of multidrug-resistant isolates of Mycobacterium tuberculosis from patients in North India. (PMID 11796356)

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)

Chan RC, et al. 2007. J Antimicrob Chemother 59(5): 866-873. Genetic and phenotypic characterization of drug-resistant Mycobacterium tuberculosis isolates in Hong Kong. (PMID 17360809)

Bahrmand AR, et al. 2009. J. Clin. Microbiol. 47(9):2744-50 High-level rifampin resistance correlates with multiple mutations in the rpoB gene of pulmonary tuberculosis isolates from the Afghanistan border of Iran. (PMID 19721079)

Prammananan T, et al. 2008. Clin. Microbiol. Infect. 14(5):446-53 Distribution of rpoB mutations among multidrug-resistant Mycobacterium tuberculosis (MDRTB) strains from Thailand and development of a rapid method for mutation detection. (PMID 18294243)

Kim BJ, et al. 1997. J. Clin. Microbiol. 35(2):492-4 Mutations in the rpoB gene of Mycobacterium tuberculosis that interfere with PCR-single-strand conformation polymorphism analysis for rifampin susceptibility testing. (PMID 9003625)

Valim AR, et al. 2000. J. Clin. Microbiol. 38(8):3119-22 Mutations in the rpoB gene of multidrug-resistant Mycobacterium tuberculosis isolates from Brazil. (PMID 10921994)

O'Sullivan DM, et al. 2005. J. Antimicrob. Chemother. 55(5):674-9 Analysis of rpoB and pncA mutations in the published literature: an insight into the role of oxidative stress in Mycobacterium tuberculosis evolution?. (PMID 15814606)

Wu X, et al. 2009. Mol. Biotechnol. 41(1):1-7 Identification of rifampin-resistant genotypes in Mycobacterium tuberculosis by PCR-reverse dot blot hybridization. (PMID 18600483)

Mani C, et al. 2001. J. Clin. Microbiol. 39(8):2987-90 Mutations in the rpoB gene of multidrug-resistant Mycobacterium tuberculosis clinical isolates from India. (PMID 11474030)

Hillemann D, et al. 2005. Antimicrob. Agents Chemother. 49(3):1229-31 Disequilibrium in distribution of resistance mutations among Mycobacterium tuberculosis Beijing and non-Beijing strains isolated from patients in Germany. (PMID 15728936)

Heym B, et al. 1994. Lancet 344(8918):293-8 Implications of multidrug resistance for the future of short-course chemotherapy of tuberculosis: a molecular study. (PMID 7914261)

Pozzi G, et al. 1999. J. Clin. Microbiol. 37(4):1197-9 rpoB mutations in multidrug-resistant strains of Mycobacterium tuberculosis isolated in Italy. (PMID 10074552)

Williams DL, et al. 1994. Antimicrob. Agents Chemother. 38(10):2380-6 Characterization of rifampin-resistance in pathogenic mycobacteria. (PMID 7840574)

Wang Q, et al. 2007. J. Proteome Res. 6(12):4564-71 A newly identified 191A/C mutation in the Rv2629 gene that was significantly associated with rifampin resistance in Mycobacterium tuberculosis. (PMID 17970586)

Aslan G, et al. 2008. Jpn. J. Infect. Dis. 61(4):255-60 Genotypic analysis of isoniazid and rifampin resistance in drug-resistant clinical Mycobacterium tuberculosis complex isolates in southern Turkey. (PMID 18653964)

Hauck Y, et al. 2009. J. Antimicrob. Chemother. 64(2):259-62 Comparison of two commercial assays for the characterization of rpoB mutations in Mycobacterium tuberculosis and description of new mutations conferring weak resistance to rifampicin. (PMID 19520715)

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)

Telenti A, et al. 1993. Lancet 341(8846):647-50 Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis. (PMID 8095569)

Bouziane F, et al. 2019. J Glob Antimicrob Resist : First genetic characterization of multi-drug resistant Mycobacterium tuberculosis isolates from Algeria. (PMID 31100498)


Prevalence of Mycobacterium tuberculosis rpoB mutants conferring resistance to rifampicin 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 tuberculosis98.77%0%72.2%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): 2300


  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB

Published Variants:

PMID in progress (multiple): L524W,T525P,H526Q,-527K Q513H,-514F,-515M,-516D -519N,S522L,S531L -515M,-516D,-517Q,-518N

PMID in progress (TB): P45S P45L E250G L430P Q432P M434I D435V D435Y D435G H445D H445Y H445L H445R S450W L452P I480V F503S L731P R827H H835R G836S Q975H I1106T

PMID: 25427352H526C S531L L533R L538R
PMID: 21300839D516V H526Y S531L
PMID: 22708343L511P M515I M515V D516V D516T D516Y H526D H526Y H526S K527Q S531L S531W S531G L533P I572F
PMID: 15047531S522L H526Y S531W
PMID: 11136757V176F Q438K D441Y D441V S447Q H451D H451R H451C H451Y S456W S456L L571V R633C E672D
PMID: 10722516V146F
PMID: 8870258A381V L521P
PMID: 12454132Q490H Q513P S522W H526R
PMID: 10423225E504A L511P Q513K Q513L D516G D516N H526L H526R
PMID: 17108078S450L S509R
PMID: 19547874S509Q Q517L L524S R528P
PMID: 15184414S512I H526N H526T R529Q
PMID: 8027320L511R S512T H526E S531C
PMID: 11796356L511V N518T S522Q K527N R528H
PMID: 10645439S512R L521M H526G
PMID: 17360809F505L S574L
PMID: 19721079G507S G507D T508H T508P T508A Q513E Q513D Q513STOP D516H N519K G523A H526F H526Q S531F
PMID: 18294243D516E,S522L D516Y,L511R S522L H526S,M515V H526S,P535H H526Y,E541G S531L,S622A
PMID: 9003625D518H
PMID: 10921994L511P,M515I L511R,D516V S531L,F514V S531L,H526C
PMID: 15814606Q513R S522STOP H526P I572F
PMID: 18600483Q517H
PMID: 11474030T508S L511M D516K N518H
PMID: 15728936V176F N518I
PMID: 10074552L511P,S512T,D516V T516I,G523W,D525Y H526D,E541G,S553A H526D,S531
PMID: 7840574H526P,K527Q
PMID: 17970586L538P
PMID: 18653964L545M
PMID: 19520715E562G,P564L
PMID: 28904673T508N S512N P520T -D516 -F514 -H526 -M515 -N518 -Q513
PMID: 31100498-S512,-Q513,-F514,H526Q


High ConfidenceS450L H445Y H445D S450L Q432P M434I D435G D435V H445Y H445R S450W P45L I480V F503S L731P R827H H835R G836S Q975H I1106T
Moderate ConfidenceH445L P45S
Minimal ConfidenceL430P D435Y L452P
Indeterminate ConfidenceE250G

>gb|CCP43410.1|+|Mycobacterium tuberculosis rpoB mutants conferring resistance to rifampicin [Mycobacterium tuberculosis H37Rv]

>gb|AL123456.3|+|759807-763325|Mycobacterium tuberculosis rpoB mutants conferring resistance to rifampicin [Mycobacterium tuberculosis H37Rv]