Mass Spectrometry-Based Targeted Metabolomics Revealed the Regulatory Roles of Magnesium on Biofilm Formation in Escherichia coli by Targeting Functional Metabolites

Biofilms often impose harmful influences in many niches involving food contamination, antibiotics resistance, and environmental issues. However, eradicating biofilms remains difficultly because the formation mechanism of biofilms is still incompletely clarified. Here, we attempted to explore the regulatory role of magnesium (Mg²⁺) on biofilm formation in Escherichia coli (E. coli) using phenotype visualization with targeted metabolomics method. We found that Mg²⁺ could exert significant influence on biofilm formation with a concentration dependency by regulating phenotypic morphology and triggering metabolic modifications of biofilm. Phenotypic imaging revealed that increasing concentration of Mg²⁺ gradually inhibited biofilm formation, Mg²⁺ was observed to restore the microstructure of E. coli strain in biofilms to that in the relevant planktonic cells. In addition, our metabolomics analysis characterized 20 differential metabolites and associated two metabolic pathways including nucleotide metabolism and amino acid metabolism that were notably modified during biofilm formation under the treatments of varied Mg²⁺. Altogether, our work provides a novel insight into the influence of Mg²⁺ on biofilm formation at a metabolic level, which is implicated in the novel solution to disturb biofilm formation through the regulation of Mg²⁺ and functional metabolite interaction.