Pseudomonas aeruginosa strain-specific outer membrane receptors (OMRs)

Pseudomonas aeruginosa strain-specific outer membrane receptors (OMRs), particularly TonB-dependent receptors (TBDTs), are critical proteins used by the bacteria to scavenge essential nutrients like iron from the host environment. In the context of cystic fibrosis (CF) lung isolates, these receptors exhibit significant diversity and strain-specific expression patterns as an adaptation to the iron-limited and highly competitive environment of the CF airway. These receptors, such as FpvA and FpvB for pyoverdine uptake, serve as vital gateways for the survival and virulence of P. aeruginosa during chronic infection. From a therapeutic perspective, these receptors are exploited as 'Trojan Horse' entry points for siderophore-drug conjugates. Drugs like Cefiderocol mimic natural siderophores to bind these OMRs, allowing the antibiotic to be actively transported across the otherwise impermeable outer membrane of Gram-negative bacteria. Because CF isolates often evolve to express specific subsets of these receptors, understanding the strain-specific landscape of OMRs is essential for predicting drug efficacy and overcoming mechanisms of resistance. These receptors represent a high-priority target for developing next-generation antimicrobials against multi-drug resistant P. aeruginosa.

Other names

TonB-dependent receptorsTBDTsOuter membrane proteinsSiderophore receptorsFerripyoverdine receptorsFpvAFpvBPfeAPirA

Siderophore-mimetic uptake via TonB-dependent receptors to bypass the outer membrane permeability barrier