Enterobactin as Part of the Oxidative Stress Response Repertoire

Abstract

Microorganisms produce siderophores to facilitate iron uptake and even though this trait has been extensively studied, there is growing evidence suggesting that siderophores may have other physiological roles aside from iron acquisition. In support of this notion, we previously linked the archetypal siderophore enterobactin with oxidative stress alleviation. To further characterize this association, we studied the sensitivity of Escherichia coli strains lacking different components of the enterobactin system to the classical oxidative stressors hydrogen peroxide and paraquat. We observed that strains impaired in enterobactin production, uptake and hydrolysis were more susceptible to the oxidative damage caused by both compounds than the wild-type strain. In addition, meanwhile iron supplementation had little impact on the sensitivity, the reducing agent ascorbic acid alleviated the oxidative stress and therefore significantly decreased the sensitivity to the stressors. This indicated that the enterobactin-mediated protection is independent of its ability to scavenge iron. Furthermore, enterobactin supplementation conferred resistance to the entE mutant but did not have any protective effect on the fepG and fes mutants. Thus, we inferred that only after enterobactin is hydrolysed by Fes in the cell cytoplasm and iron is released, the free hydroxyl groups are available for radical stabilization. This hypothesis was validated testing the ability of enterobactin to scavenge radicals in vitro. Given the strong connection between enterobactin and oxidative stress, we studied the transcription of the entE gene and the concomitant production of the siderophore in response to such kind of stress. Interestingly, we observed that meanwhile iron represses the expression and production of the siderophore, hydrogen peroxide and paraquat favour these events even if iron is present. Our results support the involvement of enterobactin as part of the oxidative stress response and highlight the existence of a novel regulation mechanism for enterobactin biosynthesis.

Bacterial Siderophores Hijack Neutrophil Functions

“…Accordingly, it was presumed that Ent may exert a plethora of key physiological functions that could account for its high metabolic cost (38), aside from acquiring iron to support bacterial growth. Such notion has been demonstrated in studies whereby Ent was shown to be fundamental for E. coli to establish colonization in the mammalian gut (39), develop mature biofilms (40, 41), alleviate oxidative stress (42, 43), and neutralize the anti-microbial activity of MPO (21). The multifaceted property of Ent is further exemplified by our findings that it could inhibit an array of neutrophil functions, including ROS generation, NETs formation, degranulation, phagocytosis and bacterial killing activity.…”

Investigation of a night soil compost psychrotrophic bacteriumGlutamicibacter arilaitensisLJH19 for its safety, efficient hydrolytic and plant growth-promoting potential

“…In previous study, it was reported that in acidic medium 2,3-dihydroxybenzoic acid (DHB), a phenolic compound consisting of catechol group which absorbs below 330 nm showing two absorption bands with maxima at 254 nm and 292 nm, respectively (Iglesias et al, 2011). DHB is an intermediate involved in the synthesis of catecholate type siderophore (Peralta et al, 2016). These evidences support the presence of DHB in LJH19 grown supernatant indicating the production of catecholate type siderophore.…”

Petrobactin protects against oxidative stress and enhances sporulation efficiency inBacillus anthracisSterne

“…, enterobactin and salmochelin) are protective against reactive oxygen species (35, 50–55). This protection is not due to iron sequestration that prevents additional Fenton reactions but is a function of the antioxidant properties of catechols (50, 53). Supplementation with free catechols doesn’t rescue the protective function of enterobactin, which requires import and hydrolysis for effective oxidative stress protection (53, 54).…”

“…This protection is not due to iron sequestration that prevents additional Fenton reactions but is a function of the antioxidant properties of catechols (50, 53). Supplementation with free catechols doesn’t rescue the protective function of enterobactin, which requires import and hydrolysis for effective oxidative stress protection (53, 54). It is unclear whether petrobactin requires additional processing to become active against oxidative stress, though the detection of petrobactin associated with spores by mass spectrometry suggests it does not.…”

“…While the demand for iron during oxidative stress and/or sporulation may relieve negative regulation by Fur, it is likely that asbA-F expression is induced by an oxidative stress regulator such as PerR. Enterobactin is positively regulated by the oxidative stress response and there is compelling evidence linking Azotobacter vinelandii catecholate siderophores to similar regulation (53–55). The observed phenotype for those siderophores is similar to that observed by Lee et al for petrobactin: high iron repression of the siderophore can be overcome by oxidative stress (35,53,55).…”