Laura Barrientos-Moreno
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María Antonia Molina-Henares
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Marta Pastor-García
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María Isabel Ramos-González
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Manuel Espinosa-Urgel
ABSTRACT
Iron is essential for most life forms. Under iron-limiting conditions, many bacteria produce and release siderophores—molecules with high affinity for iron—which are then transported into the cell in their iron-bound form, allowing incorporation of the metal into a wide range of cellular processes. However, free iron can also be a source of reactive oxygen species that cause DNA, protein, and lipid damage. Not surprisingly, iron capture is finely regulated and linked to oxidative-stress responses. Here, we provide evidence indicating that in the plant-beneficial bacterium Pseudomonas putida KT2440, the amino acid l-arginine is a metabolic connector between iron capture and oxidative stress. Mutants defective in arginine biosynthesis show reduced production and release of the siderophore pyoverdine and altered expression of certain pyoverdine-related genes, resulting in higher sensitivity to iron limitation. Although the amino acid is not part of the siderophore side chain, addition of exogenous l-arginine restores pyoverdine release in the mutants, and increased pyoverdine production is observed in the presence of polyamines (agmatine and spermidine), of which arginine is a precursor. Spermidine also has a protective role against hydrogen peroxide in P. putida, whereas defects in arginine and pyoverdine synthesis result in increased production of reactive oxygen species.
IMPORTANCE The results of this study show a previously unidentified connection between arginine metabolism, siderophore turnover, and oxidative stress in Pseudomonas putida. Although the precise molecular mechanisms involved have yet to be characterized in full detail, our data are consistent with a model in which arginine biosynthesis and the derived pathway leading to polyamine production function as a homeostasis mechanism that helps maintain the balance between iron uptake and oxidative-stress response systems.
Reactive oxygen species and enzyme dual-responsive biocompatible drug delivery system for targeted tumor therapy