Mycobacterium avium subspecies paratuberculosis DNA-directed RNA polymerase (RNAP) (MAP RNAP)

Mycobacterium avium subspecies paratuberculosis (MAP) DNA-directed RNA polymerase is an essential enzyme complex that catalyzes the transcription of bacterial DNA into messenger RNA (UniProt: P0A5I4). This enzyme is a critical component of the bacterial gene expression machinery, making it a primary target for antimicrobial therapy (PubMed: 16238959). MAP is the causative agent of Johne's disease, a chronic granulomatous enteritis in ruminants, and is also implicated in the etiology of Crohn's disease in humans (PubMed: 25038248). The enzyme's beta subunit, encoded by the rpoB gene, contains the highly conserved binding site for rifamycin-class antibiotics, including rifabutin and rifampicin (PubChem: CID 5462350). These drugs function by binding to the polymerase and sterically blocking the path of the growing RNA chain, effectively halting protein synthesis and bacterial replication (PubMed: 11514513). Because MAP is an intracellular pathogen that grows extremely slowly, targeting its transcription process is a key strategy in multi-drug regimens like RHB-104 (ClinicalTrials.gov: NCT01951326). Clinical efficacy is often monitored through the detection of MAP-specific DNA sequences, such as IS900, or host immune responses (PubMed: 10944757). However, the potential for rapid development of resistance via rpoB mutations necessitates the use of combination therapies to ensure long-term suppression of the pathogen (PubMed: 15933035).

Other names

MAP RNA polymeraseDNA-dependent RNA polymeraserpoBDNA-directed RNA polymerase subunit betaMAP_1370

Inhibition of RNA synthesis by binding to the beta subunit of the RNA polymerase, which sterically blocks the elongation of the nascent RNA transcript.