Targeted Metabolomics Revealed the Regulatory Role of Manganese on Small-Molecule Metabolism of Biofilm Formation in Escherichia coli

Biofilms are special microbial communities produced by many microorganisms, such as bacteria, viruses, and fungi. Biofilms enable the microorganisms to possess the capacity against a diversity of stressful environments. Yet, biofilm formation often causes tough challenges in clinical infections, food quality, and environmental issues, however, the formation mechanism of biofilms are still incompletely understood which seriously impedes the development of new strategies to eradicate biofilms in different niches. In this study, we sought to explore the regulatory role of manganese (Mn²⁺) on small-molecule metabolism of biofilm formation in Escherichia coli (E. coli). Using structural imaging assay combined with precision-targeted metabolomics method, to investigate how biofilm formation responded to various concentrations of Mn²⁺, we found that Mn²⁺ could inhibit biofilm formation through the regulation of phenotypic morphology and metabolic reprogramming. Collectively, our work discovered 16 differential functional metabolites and associated three metabolic pathways involving glycolysis, TCA cycle, and tryptophan metabolism that were changed mostly by Mn²⁺ during biofilm formation, which can differentiate biofilms from the relevant planktonic cells. Altogether, this study demonstrated that Mn²⁺ can inhibit biofilm formation to regulate metabolic reprogramming and micro-structure, such effort provides novel insight into the regulation of metabolic features of biofilm formation, which enables the development of new strategies to eradicate biofilm formation for addressing the challenging problems in different areas by targeting the regulation of Mn²⁺ to the biosynthesis and expressions of functional metabolites produced by different microorganisms.