Exploring copper toxicity mechanisms in Magnetospirillum gryphiswaldense MSR1 using transcriptomics

Background Magnetospirillum gryphiswaldense MSR1 biomineralizes iron into chains of magnetic nanoparticles called magnetosomes, yet remains vulnerable to copper (Cu) stress. Here, we present the first transcriptomic characterisation of the MSR1’s response to Cu, identifying coordinated changes associated with metal homeostasis, redox control and metabolic restructuring. Results Exposure to 5 ppm Cu halted exponential-phase growth within 3 h, was accompanied by an altered cellular magnetic response and reduced the proportion of healthy cells from 99 to 48%, indicating substantial membrane damage. Differential expression analysis was centred on a time-matched Cu-stress comparison, which identified 113 upregulated and 8 downregulated differentially expressed genes (DEGs; shrunken log fold change > |2 | ; Benjamini-Hochberg (BH) adjusted p- value < 1E-20). Across the full analysis, 28 genes of interest were discussed, with additional genes used for contextual support. Strong upregulation was observed in metal-handling systems including dmeRF , zntA1 and czcAB . Previous detection of CzcA in the magnetosome membrane raises the possibility that Cu handling may intersect with magnetosome-associated processes, although transcriptomic association does not establish a direct functional connection. Additional induction of redox-associated genes, including wrbA , and sulfur assimilation pathways, including cysIH , fccAB , ssuA , cysK , metZ and eamA , suggests increased demand for thiol and redox-active metabolites. Co-activation of Arsenic (As)-associated resistance genes indicated transcriptional overlap between metal-stress pathways. Conversely, genes associated with chemotaxis, respiratory activity, genome maintenance and cell envelope biosynthesis were downregulated, reflecting metabolic reallocation toward detoxification and maintenance. Gene Ontology (GO) analysis supported these trends, showing enrichment of upregulated functions associated with the TCA cycle, electron transport and protein folding, alongside enrichment of downregulated glycosyltransferase activity. Conclusions Together, these findings establish a transcriptomic framework for the Cu-stress response in MSR1 and identify candidate genes and pathways for investigating Cu tolerance and testing whether Cu stress influences magnetosome-associated processes.