Molecule Information

General Information of the Molecule (ID: Mol00940)

• Name: DNA-directed RNA polymerase subunit beta (RPOB) ,Mycobacterium tuberculosis
• Synonyms: RNAP subunit beta; RNA polymerase subunit beta; Transcriptase subunit beta; Rv0667; MTCI376.08c
• Molecule Type: Protein
• Gene Name: rpoB
• Gene ID: 888164
• Sequence:
  MLEGCILADSRQSKTAASPSPSRPQSSSNNSVPGAPNRVSFAKLREPLEVPGLLDVQTDS
  FEWLIGSPRWRESAAERGDVNPVGGLEEVLYELSPIEDFSGSMSLSFSDPRFDDVKAPVD
  ECKDKDMTYAAPLFVTAEFINNNTGEIKSQTVFMGDFPMMTEKGTFIINGTERVVVSQLV
  RSPGVYFDETIDKSTDKTLHSVKVIPSRGAWLEFDVDKRDTVGVRIDRKRRQPVTVLLKA
  LGWTSEQIVERFGFSEIMRSTLEKDNTVGTDEALLDIYRKLRPGEPPTKESAQTLLENLF
  FKEKRYDLARVGRYKVNKKLGLHVGEPITSSTLTEEDVVATIEYLVRLHEGQTTMTVPGG
  VEVPVETDDIDHFGNRRLRTVGELIQNQIRVGMSRMERVVRERMTTQDVEAITPQTLINI
  RPVVAAIKEFFGTSQLSQFMDQNNPLSGLTHKRRLSALGPGGLSRERAGLEVRDVHPSHY
  GRMCPIETPEGPNIGLIGSLSVYARVNPFGFIETPYRKVVDGVVSDEIVYLTADEEDRHV
  VAQANSPIDADGRFVEPRVLVRRKAGEVEYVPSSEVDYMDVSPRQMVSVATAMIPFLEHD
  DANRALMGANMQRQAVPLVRSEAPLVGTGMELRAAIDAGDVVVAEESGVIEEVSADYITV
  MHDNGTRRTYRMRKFARSNHGTCANQCPIVDAGDRVEAGQVIADGPCTDDGEMALGKNLL
  VAIMPWEGHNYEDAIILSNRLVEEDVLTSIHIEEHEIDARDTKLGAEEITRDIPNISDEV
  LADLDERGIVRIGAEVRDGDILVGKVTPKGETELTPEERLLRAIFGEKAREVRDTSLKVP
  HGESGKVIGIRVFSREDEDELPAGVNELVRVYVAQKRKISDGDKLAGRHGNKGVIGKILP
  VEDMPFLADGTPVDIILNTHGVPRRMNIGQILETHLGWCAHSGWKVDAAKGVPDWAARLP
  DELLEAQPNAIVSTPVFDGAQEAELQGLLSCTLPNRDGDVLVDADGKAMLFDGRSGEPFP
  YPVTVGYMYIMKLHHLVDDKIHARSTGPYSMITQQPLGGKAQFGGQRFGEMECWAMQAYG
  AAYTLQELLTIKSDDTVGRVKVYEAIVKGENIPEPGIPESFKVLLKELQSLCLNVEVLSS
  DGAAIELREGEDEDLERAAANLGINLSRNESASVEDLA
• 3D-structure: PDB ID: 6BZO; Classification: Transcription/dna/antibiotic; Method: Electron microscopy; Resolution: 3.38 Å
• Function: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
• Uniprot ID: RPOB_MYCTU

Kingdom: N.A.
Phylum: Actinobacteria
Class: Actinomycetia
Order: Corynebacteriales
Family: Mycobacteriaceae
Genus: Mycobacterium
Species: Mycobacterium tuberculosis

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

Isoniazid

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Tuberculosis [ICD-11: 1B10.0] [1]

• Resistant Disease: Tuberculosis [ICD-11: 1B10.0]
• Resistant Drug: Isoniazid
• Molecule Alteration: Mutation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis H37Rv; 83332
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: qRT-PCR
• Mechanism Description: Monoresistance to rifampicin and isoniazid was found in 11% (95% CI: 0.077-0.150; p, 0.087) and 8.5% (95% CI: 0.056-0.123; p, 0.692) of all the patients, respectively. Resistance to RIF and INH among newly diagnosed patients was 10.2% and 8.6%, while among previously treated patients, resistance to RIF and INH was 23.5% and 5.9% respectively. Furthermore, 4.9% of the samples from newly diagnosed with INH monoresistance, were found to have mutations in the InhA region while 8.6% had mutations in the katG region, a condition that can lead to phenotypic isoniazid drug resistance.

Disease Class: Urinary tuberculosis [ICD-11: 1G80.0] [2]

• Resistant Disease: Urinary tuberculosis [ICD-11: 1G80.0]
• Resistant Drug: Isoniazid
• 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: Gene sequencing assay
• Mechanism Description: Regarding drug-resistance mutation profiles, the most prevalent mutation sites were katG S315T1 and rpoB S531L.

Disease Class: Urinary tuberculosis [ICD-11: 1G80.0] [2]

• Resistant Disease: Urinary tuberculosis [ICD-11: 1G80.0]
• Resistant Drug: Isoniazid
• Molecule Alteration: Missense mutation; p.S315T1
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Gene sequencing assay
• Mechanism Description: Regarding drug-resistance mutation profiles, the most prevalent mutation sites were katG S315T1 and rpoB S531L.

Rifampin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Tuberculosis [ICD-11: 1B10.0] [1]

• Resistant Disease: Tuberculosis [ICD-11: 1B10.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Mutation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis H37Rv; 83332
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: qRT-PCR
• Mechanism Description: Monoresistance to rifampicin and isoniazid was found in 11% (95% CI: 0.077-0.150; p, 0.087) and 8.5% (95% CI: 0.056-0.123; p, 0.692) of all the patients, respectively. Resistance to RIF and INH among newly diagnosed patients was 10.2% and 8.6%, while among previously treated patients, resistance to RIF and INH was 23.5% and 5.9% respectively. Furthermore, 4.9% of the samples from newly diagnosed with INH monoresistance, were found to have mutations in the InhA region while 8.6% had mutations in the katG region, a condition that can lead to phenotypic isoniazid drug resistance.

Disease Class: Urinary tuberculosis [ICD-11: 1G80.0] [2]

• Resistant Disease: Urinary tuberculosis [ICD-11: 1G80.0]
• 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: Gene sequencing assay
• Mechanism Description: Regarding drug-resistance mutation profiles, the most prevalent mutation sites were katG S315T1 and rpoB S531L.

Disease Class: Urinary tuberculosis [ICD-11: 1G80.0] [2]

• Resistant Disease: Urinary tuberculosis [ICD-11: 1G80.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.S315T1
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• Experiment for Molecule Alteration: Gene sequencing assay
• Mechanism Description: Regarding drug-resistance mutation profiles, the most prevalent mutation sites were katG S315T1 and rpoB S531L.

References

• Ref 1: Rifampicin and isoniazid drug resistance among patients diagnosed with pulmonary tuberculosis in southwestern Uganda .PLoS One. 2021 Oct 29;16(10):e0259221. doi: 10.1371/journal.pone.0259221. eCollection 2021. 10.1371/journal.pone.0259221
• Ref 2: Clinical Features and Drug-Resistance Profile of Urinary Tuberculosis in South-Western China: A Cross-sectional Study .Medicine (Baltimore). 2016 May;95(19):e3537. doi: 10.1097/MD.0000000000003537. 10.1097/MD.0000000000003537