Pseudomonas aeruginosa arginine deiminase pathway (ADI pathway)

The Pseudomonas aeruginosa arginine deiminase (ADI) pathway is a specialized metabolic route that enables the bacterium to survive and proliferate under anaerobic or microaerophilic conditions, which are commonly encountered in the thick mucus of cystic fibrosis lungs and within mature biofilms [Source: Yoon et al., 2002, Journal of Bacteriology]. The pathway consists of three primary enzymes: arginine deiminase (ArcA), ornithine carbamoyltransferase (ArcB), and carbamate kinase (ArcC), which collectively convert L-arginine into L-ornithine, ammonia, and carbon dioxide, yielding one mole of ATP per mole of arginine [Source: Vander Wauven et al., 1984, Journal of Bacteriology]. Beyond energy production, the release of ammonia serves to neutralize acidic metabolic byproducts, thereby maintaining pH homeostasis and enhancing bacterial persistence in hostile environments [Source: Xu et al., 2003, Applied and Environmental Microbiology]. As this pathway is essential for the chronic infection phenotype of P. aeruginosa and is distinct from human metabolic pathways, it represents a significant target for the development of narrow-spectrum antibacterial agents [Source: Lu et al., 2004, Journal of Bacteriology]. Therapeutic strategies typically involve the use of arginine analogs or small-molecule inhibitors designed to block ArcA activity, effectively depleting the bacteria of energy in low-oxygen niches [Source: Gao et al., 2018, Molecules].

Other names

Arc pathwayArginine deiminase systemADI systemArginine catabolic pathway

Inhibition of the enzymes ArcA, ArcB, or ArcC to prevent anaerobic ATP production and disrupt pH regulation, leading to decreased bacterial viability and biofilm stability in hypoxic environments [Source: Gao et al., 2018, Molecules].