Vanadium interferes with siderophore-mediated iron uptake in Pseudomonas aeruginosa

Vanadium is a metal that under physiological conditions can exist in two ox idation slates, V(IV) (vanadyl ion) and V(V) (vanadate ion). Here, it was d emonstrated that both ions can form complexes with siderophores. Pseudomona s aeruginosa produces two siderophores under iron-limiting conditions, pyov erdine (PVD) and pyochelin (PCH). Vanadyl sulfate, at a concentration of 1- 2 mM, strongly inhibited growth of P. aeruginosa PAO1, especially under con ditions of severe iron limitation imposed by the presence of non-utilizable Fe(lll) chelators. PVD-deficient mutants were more sensitive to vanadium t han the wild-type, but addition of PVD did not stimulate their growth. Conv ersely, PCH-negative mutants were more resistant to vanadium than the wild- type strain. Both siderophores could bind and form complexes with vanadium after incubation with vanadyl sulfate (1:1, in the case of PVD; 2:1, in the case of PCH), Although only one complex with PVD, V(IV)-PVD, was found, bo th V(IV)- and V(V)-PCH were detected. V-PCH, but not V-PVD, caused strong g rowth reduction, resulting in a prolonged lag phase. Exposure of PAO1 cells to vanadium induced resistance to the superoxide-generating compound paraq uat, and conversely, exposure to paraquat increased resistance to V(IV). Su peroxide dismutase (SOD) activity of cells grown in the presence of V(IV) w as augmented by a factor of two. Mutants deficient in the production of Fe- SOD (SodB) were particularly sensitive to vanadium, whilst sodA mutants def icient for Mn-SOD were only marginally affected. In conclusion, it is sugge sted that V-PCH catalyses a Fenton-type reaction whereby the toxic superoxi de anion O-2(-) is generated, and that vanadium compromises PVD utilization .