TonB-dependent iron receptor (TBDR)

Pseudomonas aeruginosa iron-transport receptors, primarily the TonB-dependent receptors (TBDRs), are essential outer membrane proteins that facilitate the acquisition of iron from the host environment [1, 7]. Iron is a critical nutrient for bacterial growth and virulence, but its availability is limited in the host by sequestering proteins like transferrin and lactoferrin [7, 18]. To overcome this, P. aeruginosa secretes siderophores such as pyoverdine and pyochelin and expresses specific TBDRs like FpvA, FptA, PiuA, and PirA to actively transport iron-siderophore complexes into the cell [8, 17]. Additionally, the bacterium utilizes heme receptors like PhuR and HasR to acquire iron from host hemoproteins [4, 17]. These receptors are exploited by "Trojan horse" antibiotics like cefiderocol, which conjugate a siderophore-like moiety to a beta-lactam core to bypass traditional resistance mechanisms [6, 8]. The active transport of these conjugates through TBDRs allows the drug to reach its periplasmic targets even in the presence of porin loss or efflux pump upregulation [6, 13]. However, mutations in these receptors or their regulatory genes, such as pirR, can lead to reduced drug uptake and the emergence of resistance or heteroresistance [9, 13]. Therapeutic strategies also include the use of iron mimics like gallium, which compete for transport through these systems to disrupt bacterial metabolism [18, 19]. Understanding the diversity and redundancy of these transport systems is crucial for developing effective treatments against multidrug-resistant P. aeruginosa [8, 19].

Other names

Siderophore receptorFerripyoverdine receptorFerripyochelin receptorHeme receptorOuter membrane iron transporterTonB-dependent transporterTBDT

Siderophore-mediated active transport (Trojan horse strategy)