Pseudomonas aeruginosa, a common nosocomial pathogen, relies on
siderophores to acquire
iron, crucial for its survival in various environments and during host
infections. However, understanding the molecular mechanisms of
siderophore regulation remains incomplete. In this study, we found that the BfmRS two-component system, previously associated with biofilm formation and quorum sensing, is essential for
siderophore regulation under high osmolality stress. Activated BfmR directly bound to the promoter regions of pvd, fpv, and femARI gene clusters, thereby activating their transcription and promoting
siderophore production. Subsequent proteomic and phenotypic analyses confirmed that deletion of BfmRS reduces
siderophore-related
proteins and impairs bacterial survival in
iron-deficient conditions. Furthermore, phylogenetic analysis demonstrated the high conservation of the BfmRS system across Pseudomonas species, functional evidences also indicated that BfmR homologues from Pseudomonas putida KT2440 and Pseudomonas sp. MRSN12121 could bind to the promoter regions of key
siderophore genes and osmolality-mediated increases in
siderophore production were observed. This work illuminates a novel signaling pathway for
siderophore regulation and enhances our understanding of
siderophore-mediated bacterial interactions and community establishment.