Work

Identification of iron and zinc responsive TonB-dependent transporters in Pseudomonas aeruginosa

Year: 2026

Type: article

Abstract: Pseudomonas aeruginosa employs a repertoire of TonB-dependent transporters (TBDTs) to acquire essential nutrients, such as iron-siderophore complexes, enabling its adaptation to diverse and often hostile environments. While the roles of some TBDTs in virulence and metal acquisition are well-established, many remain poorly characterized, despite their potential contributions to pathogenicity. Using a domain-based detection approach, we show that TBDTs are broadly conserved across diverse P. aeruginosa isolates and remain highly prevalent in multidrug-resistant (MDR) strains, highlighting their potential as robust therapeutic entry points. Notably, these transporters can be exploited for antibiotic delivery, as exemplified by the siderophore-antibiotic conjugate cefiderocol. To identify TBDTs involved in metal uptake, we combined bioinformatic promoter analysis with fluorescent transcriptional reporters to monitor their response to iron and zinc limitation. This approach identified 21 iron-responsive and 4 zinc-responsive TBDTs, including transporters with previously unknown substrates, and revealed that promoter-associated regulatory motifs, rather than protein homology, predict metal-specific regulation. Beyond classification, these fluorescent reporter constructs serve as a versatile tool for exogenous siderophore detection by monitoring transporter activity in response to their presence. Furthermore, single-cell analysis of TBDT promoter activity during co-culture with an enterobactin-producing Klebsiella pneumoniae strain revealed homogeneous expression of key TBDTs in P. aeruginosa populations, suggesting coordinated metal acquisition strategies under competitive conditions.

Source: BioMetals

DOI: 10.1007/s10534-026-00880-0