Bacterial RNA Polymerase Inhibition Module

Module bacterial_rna_polymerase_inhibition 2 disorders Pathograph 2

A conserved antibacterial drug-mechanism module representing bacterial DNA-dependent RNA polymerase (RNAP), the enzyme that transcribes mRNA and the target of the rifamycin class (rifampicin, rifabutin, rifapentine, rifaximin). Rifamycins bind the RNAP beta subunit (encoded by rpoB) in the DNA/RNA channel and block extension of nascent RNA beyond a few nucleotides, halting transcription. Because the bacterial RNAP sequence diverges from the human enzyme, rifamycins are selectively toxic. Rifamycins penetrate cells and biofilms well and are a backbone of antimycobacterial therapy and of regimens for intracellular and device-associated infection — but because single rpoB point mutations confer high-level resistance, they are almost always used in combination. This module defines the mechanism-of-action design pattern for rifamycin treatments: conforming entries link a treatment to the RNAP target via target_mechanisms.

⚙

Pathophysiology Nodes

2 shared nodes are defined in this module.

◉

Cell Types

No cell types are annotated for this module.

⇄

Biological Processes

Notes

Antibacterial drug-mechanism module, not a specific disease. Disorder entries reference nodes via conforms_to (e.g., "bacterial_rna_polymerase_inhibition#Bacterial RNA Polymerase (Rifamycin Target)"), and their rifamycin treatments point at that node via target_mechanisms. Key conformance / treatment target: "Bacterial RNA Polymerase (Rifamycin Target)". The rpoB-mutation resistance node is the reason rifamycins are given in combination — relevant to mycobacterial regimens. Nodes are druggable steps, not individual drugs.

↗

Used By Disorder Entries

Buruli ulcer via Mycobacterial RNA Polymerase (Rifampicin Target) → Bacterial RNA Polymerase (Rifamycin Target)

Leprosy via Mycobacterial RNA Polymerase (Rifampicin Target) → Bacterial RNA Polymerase (Rifamycin Target)

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence-backed metadata.

⚙

Pathophysiology

Bacterial RNA Polymerase (Rifamycin Target)

therapeutic vulnerability

Bacterial DNA-dependent RNA polymerase (RNAP) performs the first step of gene expression, transcribing DNA into RNA. Rifamycins bind the RpoB (beta) subunit within the RNA exit channel and sterically block elongation of the nascent RNA chain past 2-3 nucleotides, arresting transcription. The bacterial RNAP sequence diverges sufficiently from the human enzyme to make this target selective, and rifamycins penetrate host cells and biofilms well, extending their utility to mycobacterial, intracellular, and device-associated infection.

DNA-Templated Transcription GO:0006351

Used by disorders

Buruli ulcer as Mycobacterial RNA Polymerase (Rifampicin Target)

Leprosy as Mycobacterial RNA Polymerase (Rifampicin Target)

Downstream

rpoB-Mediated Rifamycin Resistance Single rpoB point mutations confer high-level resistance, which is why rifamycins are used in combination.

rpoB-Mediated Rifamycin Resistance

adaptive escape

Resistance to rifamycins arises predominantly from point mutations in a short, conserved region of the rpoB gene encoding the RNA polymerase beta subunit, which reduce drug binding. Because a single chromosomal mutation can confer high-level resistance and emerges readily under monotherapy, rifamycins are given as part of combination regimens (e.g. with isoniazid/other agents in mycobacterial disease, or with a second agent in staphylococcal device-associated infection). rpoB mutation is also the molecular basis of the GeneXpert rifampicin-resistance diagnostic in tuberculosis.

Response to Antibiotic GO:0046677