Arginine deiminase pathway enzymes (ADI pathway enzymes)

The arginine deiminase (ADI) pathway in Pseudomonas aeruginosa is a three-enzyme system consisting of arginine deiminase (ArcA), ornithine carbamoyltransferase (ArcB), and carbamate kinase (ArcC) (UniProt: P0A3T0, P0A3T3, P0A3T7). This pathway is essential for the bacterium's survival under anaerobic or microaerophilic conditions, such as those found in the thick mucus of cystic fibrosis patients or within deep biofilm layers (PubMed: 15252015). By catabolizing L-arginine, the pathway generates one mole of ATP per mole of arginine and produces ammonia, which helps the pathogen resist acidic stress (PubMed: 16109944). The ADI pathway is highly upregulated during biofilm growth and is a key factor in the persistence of chronic infections. Because the ADI pathway is absent in humans but critical for P. aeruginosa persistence and virulence, it represents a promising target for the development of narrow-spectrum antibiotics. Inhibiting these enzymes can lead to energy depletion and increased sensitivity to environmental stressors, potentially clearing chronic infections that are otherwise resistant to conventional treatments (PubMed: 21664334). Experimental inhibitors like L-canavanine have shown potential in disrupting this metabolic route. Targeting this pathway offers a strategy to combat multidrug-resistant strains by focusing on metabolic vulnerabilities specific to the infection environment.

Other names

ArcABC systemArginine catabolic pathwayADI systemArc operon enzymes

Inhibition of anaerobic energy production and acid resistance by blocking the conversion of arginine to ATP and ammonia.