Molecule Information

General Information of the Molecule (ID: Mol02138)

• Name: DNA-directed RNA polymerase subunit beta (RPOB) ,Clostridioides difficile
• Synonyms: DNA-directed RNA polymerase subunit beta (RPOB)
• Molecule Type: Protein

Kingdom: N.A.
Phylum: Firmicutes
Class: Clostridia
Order: Eubacteriales
Family: Peptostreptococcaceae
Genus: Clostridioides
Species: Clostridioides difficile

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Fidaxomicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Clostridium difficile infection [ICD-11: 1A04.0] [1]

• Resistant Disease: Clostridium difficile infection [ICD-11: 1A04.0]
• Resistant Drug: Fidaxomicin
• Molecule Alteration: Mutation; p.E1073K+p.Q1074K+p.V1143F
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: Despite both drugs share a common target, the nucleotide substitution within rpoB of fidaxomicin and RIF-resistant strains locate differently. In vitro study has revealed that amino acid substitutions in either rpoB at E1073K, Q1074K and V1143F or rpoC at D273Y confer resistance to fidaxomicin.

Rifampin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Clostridium difficile infection [ICD-11: 1A04.0] [1]

• Resistant Disease: Clostridium difficile infection [ICD-11: 1A04.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Mutation; p.R505K
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: RIFs (rifampicin and rifaximin) have recently been used as another option for CDI treatment. Nevertheless, the resistance to RIFs in C. difficile has been reported. These drugs target on a DNA-dependent RNA polymerase (RNAP), resulting in the extension of short transcript blockage. Point mutations within the rpoB gene encoding for beta-subunit of RNAP cause resistance to RIFs. Among identified amino acid substitutions, the R505K substitution has been mostly evident to promote the high level of resistance.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Tuberculosis [ICD-11: 1B10.0] [2]

• Resistant Disease: Tuberculosis [ICD-11: 1B10.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Mutation; R173C
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: GeneSeq assay; Bioinformatics assay
• Mechanism Description: Out of total 112 mycobacterial positive cultures, five?M. bovis?were isolated and underwent WGS. All sequenced strains belonged to?Mycobacterium tuberculosis var bovis, spoligotype BOV_1; BOV_11. Resistance gene mutations were determined in 100% of strains to pyrazinamide (pncA?and?rpsA), isoniazid (KatG?and?ahpC), ethambutol (embB,?embC,?embR?and?ubiA), streptomycin (rpsl) and fluoroquinolones (gyrA?and?gyrB). Rifampin (rpoB?and?rpoC) and delamanid (fbiC) resistance genes were found in 80% of strains. The major represented virulence classes were the secretion system, cell surface components and regulation system.

Rifaximin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Clostridium difficile infection [ICD-11: 1A04.0] [1]

• Resistant Disease: Clostridium difficile infection [ICD-11: 1A04.0]
• Resistant Drug: Rifaximin
• Molecule Alteration: Mutation; p.R505K
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: RIFs (rifampicin and rifaximin) have recently been used as another option for CDI treatment. Nevertheless, the resistance to RIFs in C. difficile has been reported. These drugs target on a DNA-dependent RNA polymerase (RNAP), resulting in the extension of short transcript blockage. Point mutations within the rpoB gene encoding for beta-subunit of RNAP cause resistance to RIFs. Among identified amino acid substitutions, the R505K substitution has been mostly evident to promote the high level of resistance.

References

• Ref 1: Insights into drug resistance mechanisms in Clostridium difficile .Essays Biochem. 2017 Mar 3;61(1):81-88. doi: 10.1042/EBC20160062. Print 2017 Feb 28. 10.1042/EBC20160062
• Ref 2: Genetic diversities and drug resistance in Mycobacterium bovis isolates from zoonotic tuberculosis using whole genome sequencing. BMC Genomics. 2024 Nov 1;25(1):1024.