OprD and OprH Porins: Key Gateways in Antimicrobial Resistance of Pseudomonas aeruginosa

The opportunistic Gram-negative bacterium Pseudomonas aeruginosa is recognized for its innate and acquired resistance to a broad range of drugs. It is a primary contributor to nosocomial infections due to its versatility and persistence in clinical settings, especially in those with compromised immune systems. This pathogen is characterized by an exterior membrane that prevents molecules from entering the cell. Porins, which are outer membrane water-filled protein channels, aid in the intake of nutrients and are believed to allow the entry of antibiotics. In its outer membrane, alteration in porins proteins is involved in its resistance mechanisms. OprD and OprH which control antibiotic entry are important among them. OprD and OprH with their regulatory pathways are thoroughly summarised in this review article because of their central role in antibiotic resistance mechanism. OprD involved in carbapenems and basic amino acids uptake; resistance to imipenem and carbapenems is closely linked to its downregulation or loss. OprH increases in magnesium-limiting environments, stabilizing the outer membrane and altering lipopolysaccharide charge, providing resistance to cationic antimicrobial peptides like polymyxins. This review thoroughly discusses functions of OprD and OprH, their regulatory mechanisms, and their role in P. aeruginosa's complex antibiotic resistance profile. To address the present antimicrobial resistance challenge, new antibiotics are desperately needed. The main obstacle in the creation of potent new antibiotics for important infections is drug penetration through the cell membrane. Furthermore, developing focused tactics to fight multidrug-resistant P. aeruginosa infections requires an understanding of these porin-mediated pathways. Additionally, it offers significant therapeutic implications for addressing the inducible basis of resistance.