Molecule Information

General Information of the Molecule (ID: Mol00941)

• Name: DNA-directed RNA polymerase subunit beta (RPOB) ,Escherichia coli
• Synonyms: RNAP subunit beta; RNA polymerase subunit beta; Transcriptase subunit beta; groN; nitB; rif; ron; stl; stv; tabD; b3987; JW3950
• Molecule Type: Protein
• Gene Name: rpoB
• Gene ID: 67415312
• Sequence:
  MVYSYTEKKRIRKDFGKRPQVLDVPYLLSIQLDSFQKFIEQDPEGQYGLEAAFRSVFPIQ
  SYSGNSELQYVSYRLGEPVFDVQECQIRGVTYSAPLRVKLRLVIYEREAPEGTVKDIKEQ
  EVYMGEIPLMTDNGTFVINGTERVIVSQLHRSPGVFFDSDKGKTHSSGKVLYNARIIPYR
  GSWLDFEFDPKDNLFVRIDRRRKLPATIILRALNYTTEQILDLFFEKVIFEIRDNKLQME
  LVPERLRGETASFDIEANGKVYVEKGRRITARHIRQLEKDDVKLIEVPVEYIAGKVVAKD
  YIDESTGELICAANMELSLDLLAKLSQSGHKRIETLFTNDLDHGPYISETLRVDPTNDRL
  SALVEIYRMMRPGEPPTREAAESLFENLFFSEDRYDLSAVGRMKFNRSLLREEIEGSGIL
  SKDDIIDVMKKLIDIRNGKGEVDDIDHLGNRRIRSVGEMAENQFRVGLVRVERAVKERLS
  LGDLDTLMPQDMINAKPISAAVKEFFGSSQLSQFMDQNNPLSEITHKRRISALGPGGLTR
  ERAGFEVRDVHPTHYGRVCPIETPEGPNIGLINSLSVYAQTNEYGFLETPYRKVTDGVVT
  DEIHYLSAIEEGNYVIAQANSNLDEEGHFVEDLVTCRSKGESSLFSRDQVDYMDVSTQQV
  VSVGASLIPFLEHDDANRALMGANMQRQAVPTLRADKPLVGTGMERAVAVDSGVTAVAKR
  GGVVQYVDASRIVIKVNEDEMYPGEAGIDIYNLTKYTRSNQNTCINQMPCVSLGEPVERG
  DVLADGPSTDLGELALGQNMRVAFMPWNGYNFEDSILVSERVVQEDRFTTIHIQELACVS
  RDTKLGPEEITADIPNVGEAALSKLDESGIVYIGAEVTGGDILVGKVTPKGETQLTPEEK
  LLRAIFGEKASDVKDSSLRVPNGVSGTVIDVQVFTRDGVEKDKRALEIEEMQLKQAKKDL
  SEELQILEAGLFSRIRAVLVAGGVEAEKLDKLPRDRWLELGLTDEEKQNQLEQLAEQYDE
  LKHEFEKKLEAKRRKITQGDDLAPGVLKIVKVYLAVKRRIQPGDKMAGRHGNKGVISKIN
  PIEDMPYDENGTPVDIVLNPLGVPSRMNIGQILETHLGMAAKGIGDKINAMLKQQQEVAK
  LREFIQRAYDLGADVRQKVDLSTFSDEEVMRLAENLRKGMPIATPVFDGAKEAEIKELLK
  LGDLPTSGQIRLYDGRTGEQFERPVTVGYMYMLKLNHLVDDKMHARSTGSYSLVTQQPLG
  GKAQFGGQRFGEMEVWALEAYGAAYTLQEMLTVKSDDVNGRTKMYKNIVDGNHQMEPGMP
  ESFNVLLKEIRSLGINIELEDE
• Function: DNA-dependent RNA polymerase (RNAP) catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
• Uniprot ID: RPOB_ECOLI

Kingdom: N.A.
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Enterobacterales
Family: Enterobacteriaceae
Genus: Escherichia
Species: Escherichia coli

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Rifampin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Bacterial infection [1], [2]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; c.ins1593C
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli MG1655; 511145
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Frameshift mutations have been reported in rpoB, an essential gene encoding the beta-subunit of RNA polymerase, in rifampicin-resistant clinical isolates of Mycobacterium tuberculosis. Escherichia coli with a +1-nt frameshift mutation centrally located in rpoB is viable and highly resistant to rifampicin.

Disease Class: HIV-infected patients with tuberculosis [3], [4], [5]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.L511P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.

Disease Class: HIV-infected patients with tuberculosis [3], [4], [5]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.Q513P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.

Disease Class: HIV-infected patients with tuberculosis [3], [4], [5]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.Q513K
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.

Disease Class: HIV-infected patients with tuberculosis [3], [4], [5]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.D516V
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.

Disease Class: HIV-infected patients with tuberculosis [3], [4], [5]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.H526N+p.L533P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.

Disease Class: HIV-infected patients with tuberculosis [3], [4], [5]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.H526Y
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.

Disease Class: HIV-infected patients with tuberculosis [3], [4], [5]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.H526R
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.

Disease Class: HIV-infected patients with tuberculosis [3], [4], [5]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.H526D
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.

Disease Class: HIV-infected patients with tuberculosis [3], [4], [5]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.H526N
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.

Disease Class: HIV-infected patients with tuberculosis [3], [4], [5]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.H526L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.

Disease Class: HIV-infected patients with tuberculosis [3], [4], [5]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.H526C
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.

Disease Class: HIV-infected patients with tuberculosis [3], [4], [5]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.S531W
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.

Disease Class: HIV-infected patients with tuberculosis [3], [4], [5]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.S531L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.

Disease Class: HIV-infected patients with tuberculosis [3], [4], [5]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.L533P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.

Disease Class: HIV-infected patients with tuberculosis [3], [4], [5]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.E562G+p.P564L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.

Disease Class: HIV-infected patients with tuberculosis [3], [4], [5]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Frameshift mutation; c.513_516del*AA TTC ATG G*
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.

Tedizolid

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Gram-negative bacterial infection [6]

• Resistant Disease: Gram-negative bacterial infection [ICD-11: 1B74-1G40]
• Resistant Drug: Tedizolid
• Molecule Alteration: Missense mutation; p.A1345G
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Gram-positive bacteria MRSA strain N315; .
• Experiment for Molecule Alteration: Whole-genome sequencing assay
• Mechanism Description: Tedizolid resistance is uncommon and tedizolid's capacity to select for cross-resistance to other antimicrobials is incompletely understood. To the best of our knowledge, this is the first time that an rpoB mutation has been implicated in resistance to PhLOPSa antimicrobials.

References

• Ref 1: Mapping and sequencing of mutations in the Escherichia coli rpoB gene that lead to rifampicin resistance. J Mol Biol. 1988 Jul 5;202(1):45-58. doi: 10.1016/0022-2836(88)90517-7.
• Ref 2: Antibiotic resistance by high-level intrinsic suppression of a frameshift mutation in an essential gene. Proc Natl Acad Sci U S A. 2020 Feb 11;117(6):3185-3191. doi: 10.1073/pnas.1919390117. Epub 2020 Jan 28.
• Ref 3: rpoB mutations in multidrug-resistant strains of Mycobacterium tuberculosis isolated in Italy. J Clin Microbiol. 1999 Apr;37(4):1197-9. doi: 10.1128/JCM.37.4.1197-1199.1999.
• Ref 4: Universal pattern of RpoB gene mutations among multidrug-resistant isolates of Mycobacterium tuberculosis complex from Africa. Int J Tuberc Lung Dis. 1999 Jul;3(7):620-6.
• Ref 5: Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. Tuber Lung Dis. 1998;79(1):3-29. doi: 10.1054/tuld.1998.0002.
• Ref 6: Identification of a novel tedizolid resistance mutation in rpoB of MRSA after in vitro serial passage .J Antimicrob Chemother. 2021 Jan 19;76(2):292-296. doi: 10.1093/jac/dkaa422. 10.1093/jac/dkaa422