Catecholate Siderophores Protect Bacteria from Pyochelin Toxicity

Abstract

BackgroundBacteria produce small molecule iron chelators, known as siderophores, to facilitate the acquisition of iron from the environment. The synthesis of more than one siderophore and the production of multiple siderophore uptake systems by a single bacterial species are common place. The selective advantages conferred by the multiplicity of siderophore synthesis remains poorly understood. However, there is growing evidence suggesting that siderophores may have other physiological roles besides their involvement in iron acquisition.Methods and Principal FindingsHere we provide the first report that pyochelin displays antibiotic activity against some bacterial strains. Observation of differential sensitivity to pyochelin against a panel of bacteria provided the first indications that catecholate siderophores, produced by some bacteria, may have roles other than iron acquisition. A pattern emerged where only those strains able to make catecholate-type siderophores were resistant to pyochelin. We were able to associate pyochelin resistance to catecholate production by showing that pyochelin-resistant Escherichia coli became sensitive when biosynthesis of its catecholate siderophore enterobactin was impaired. As expected, supplementation with enterobactin conferred pyochelin resistance to the entE mutant. We observed that pyochelin-induced growth inhibition was independent of iron availability and was prevented by addition of the reducing agent ascorbic acid or by anaerobic incubation. Addition of pyochelin to E. coli increased the levels of reactive oxygen species (ROS) while addition of ascorbic acid or enterobactin reduced them. In contrast, addition of the carboxylate-type siderophore, citrate, did not prevent pyochelin-induced ROS increases and their associated toxicity.ConclusionsWe have shown that the catecholate siderophore enterobactin protects E. coli against the toxic effects of pyochelin by reducing ROS. Thus, it appears that catecholate siderophores can behave as protectors of oxidative stress. These results support the idea that siderophores can have physiological roles aside from those in iron acquisition.

The Siderophore Metabolome of Azotobacter vinelandii

“…Structural variation of siderophores may also allow the organism to optimize uptake depending on environmental Fe chemistries (58), facilitate uptake of other required metals (e.g., Mo and V), or sequester toxic metals (e.g., W) (10). Siderophores may also act as redox shuttles, even as signaling molecules, and can serve multiple functions simultaneously (59). This leads to a fundamental reason for the vast structural variation: siderophore structures could result from multiple selective pressures that reflect evolutionary arms races including not just competition for low-abundance catalytic metals but also other processes.…”

Links between Anr and Quorum Sensing in Pseudomonas aeruginosa Biofilms

“…Multiple genes involved in the oxidative stress response (katB, which encodes a catalase, as well as ahpB and ahpCF, which encode hydroperoxide reductases) were expressed at a level Ͼ2-fold higher in both the PAO1 and J215 ⌬anr mutants. Quinolines have been shown to sensitize P. aeruginosa to oxidative stress (79), and pyochelin can promote oxidative stress (80) and is regulated in response to oxidative stress (81).…”

Influence of Niche-Specific Nutrients on Secondary Metabolism in Vibrionaceae

“…4). Siderophores similar to fluvibactin can inhibit bacterial and fungal growth (20,56), and catechol iron chelators have also been suggested to protect bacteria from oxidative stress (57,58). Hence, beside the competitive advantage during surface colonization due to the antibacterial activity of fluvibactin, producers of this compound might as well be protected from oxidative stress, which is a prevalent phenomenon in the marine environment (59).…”