Deletion of <i>tonB1</i> in <i>Pseudomonas aeruginosa</i> impairs zinc homeostasis and pathogenicity

Zinc is the second most abundant metal element in cells, and it plays an important role in the pathogenicity and antibiotic resistance of pathogenic bacteria. <i>Pseudomonas aeruginosa</i> is an increasingly prevalent and multidrug-resistant pathogen that relies on TonB proteins for transporting numerous nutrients. Herein, we revealed that TonB1 is essential for zinc homeostasis in <i>P. aeruginosa</i>; its deletion severely impaired bacterial growth under zinc limitation and was associated with reduced intracellular zinc levels and dysregulation of zinc uptake-related genes-potentially contributing to heightened susceptibility to host defenses (e.g., calprotectin), oxidative stress, and loss of motility and infectivity. This discovery highlights a critical role for TonB1 in maintaining zinc homeostasis, which impacts pathogenicity in <i>P. aeruginosa</i>. Although TonB homologs have been implicated in zinc uptake elsewhere, our work demonstrates that it is indispensable for virulence in this pathogen, significantly expanding the understanding of TonB's physiological functions beyond iron uptake and highlighting a key adaptation mechanism for essential metal nutrients.