Nickel exposure reduces enterobactin production in Escherichia coli. Original paper

What was studied?

Nickel exposure reduces enterobactin production in Escherichia coli by blocking the normal rise of this catecholate siderophore during iron-limited growth. The authors investigated whether nickel contributes to the longer lag phase and iron starvation by limiting extracellular enterobactin, even as cells activate iron uptake genes. They tracked growth, intracellular metals, siderophore levels, and promoter activity to connect nickel stress with a drop in secreted enterobactin and a shortfall in iron delivery. This work identifies nickel as a metal signal that reshapes siderophore output and iron balance in Enterobacterales, which is important for both environmental and host niches.

Who was studied?

The team used Escherichia coli MG1655 in defined minimal media with background iron in the nanomolar range and added NiCl₂ from 0 to 50 μM. They measured intracellular Fe, Ni, Zn, Mn, and Cu by ICP-MS, quantified catecholate siderophores in culture supernatants by the Arnow assay and FPLC, and read iron-responsive promoters with lacZ fusions for fepA, sufA, and iscR. A ΔfepA mutant helped test whether lower extracellular catechols reflect faster re-uptake rather than reduced production. This design separated transcriptional responses from actual siderophore supply in the medium that supports iron import.

Most important findings

Nickel prolonged lag phase without large effects on later growth and blocked the normal rise in intracellular iron during lag, while cells accumulated nickel and modestly increased zinc. Despite that iron need, nickel kept fepA, sufA, and iscR expression high, showing a clear iron-starvation response. Yet extracellular catechols fell in a nickel-dose-dependent way, and FPLC showed that enterobactin and each hydrolysis product declined with nickel. The ΔfepA strain also showed reduced extracellular catechols under nickel, which rules out faster FepA-mediated import as the cause and supports impaired production or export.

Together, these data explain why iron uptake fails under nickel stress: siderophore supply outside the cell drops even as demand rises. The study also situates this effect within broader metal cross-talk noted for catecholates, which can increase copper toxicity by driving Cu(II) to Cu(I); nickel therefore not only limits iron capture but may change copper risk by lowering catecholate output in mixed-metal settings relevant to inflamed mucosa. For a microbiome signatures database, this yields practical markers: entCEBA/entS pathway activity and extracellular catechols as readouts of iron supply, with nickel exposure as a modifier that predicts transient iron starvation in Enterobacterales.

Key implications

Clinicians can read nickel as a metal stressor that delays E. coli adaptation by cutting extracellular enterobactin and pushing iron starvation, even when iron uptake genes stay on. In host settings that raise nickel—industrial exposures, devices, or diets—Enterobacterales may show a lag in iron acquisition with downstream shifts in growth and competition. Reporting entCEBA, entS, and fepA status with measured or inferred nickel exposure can help explain low-iron signals and guide metal-aware care. Because catecholate loss also blunts copper redox cycling, nickel may transiently lower copper injury from catechols while still limiting iron, a trade-off that could favor strains that switch to non-catecholate metallophores. Embedding these gene modules and metal context in microbiome reports can refine risk calls for Enterobacterales dominance in stressed urine or gut and support targeted mitigation that avoids adding metals that worsen imbalance.