Increasing the copper sensitivity of microorganisms by restricting iron supply, a strategy for bio‐management practices Original paper

What was studied?

This study tested increasing the copper sensitivity of microorganisms by restricting iron supply as a way to lower the copper dose needed to control bacteria. The authors mapped how copper overload damages iron–sulfur enzymes, triggers an iron-starvation signal, and drives bacteria to import iron to rebuild damaged clusters. They then asked whether blocking iron uptake would remove this safety valve and make cells far more sensitive to copper or cadmium. The work linked copper stress to induction of iron transport genes, shifts in superoxide dismutase activity, and markers of porphyrin pathway damage, and it framed a practical bio-management strategy that pairs low copper with iron limitation.

Who was studied?

The primary model was the purple bacterium Rubrivivax gelatinosus carrying targeted defects in copper or cadmium efflux pumps (CopA or CadA) and in iron import systems (FbpABC and the Ftr pathway). The team validated the concept in Vibrio cholerae by combining a copA deletion with loss of the periplasmic iron-binding protein FbpA, and they profiled Escherichia coli efflux mutants to track superoxide dismutase responses to copper or cadmium. These species span environmental and enteric pathogens and capture microbiome-relevant traits such as siderophore use and oxidative stress control.

Most important findings

Limiting iron uptake sharply increased copper or cadmium killing. In R. gelatinosus, disrupting fbpA or fbpBC in efflux-defective strains caused growth arrest with copper concentrations that the parent strains tolerated, and combining fbpA and ftrA defects heightened sensitivity further. Copper stress induced fbpA and ftrA expression and reduced cellular iron in efflux mutants, which shows that cells perceive iron lack during metal overload. Release of coproporphyrin III signaled copper injury to iron–sulfur enzymes, and Fe-S repair demands likely drove the iron-uptake response. In V. cholerae, the copA fbpA double mutant showed stronger copper sensitivity than either single mutant, confirming the role of iron import in defense. In E. coli, copper or cadmium accumulation shifted superoxide dismutase activity from Fe-Sod to Mn-Sod, consistent with iron dysregulation under metal stress.

Key implications

Clinicians and agronomists can pair copper exposure with iron limitation to lower required copper, reduce environmental load, and still suppress target microbes. For microbiome tracking, expect decreased survival of Enterobacterales and Vibrio-like taxa when iron import is constrained under copper pressure, with gene signatures that include downshifted fbpABC or ftr transcripts and stress markers such as sodB upregulation. This work also echoes host nutritional immunity, which withholds iron while flooding phagosomes with copper; therapeutics that inhibit siderophore uptake or Fbp/Ftr transporters could potentiate host copper defenses without raising metal doses. Because heavy metals can co-select antibiotic resistance, strategies that achieve control with less copper are desirable. These data provide a mechanistic basis and specific microbial targets to build microbiome-aware, metal-sparing interventions.