Zinc effects on bacteria: insights from Escherichia coli by multi-omics approach.

In this study, we investigated the impact of zinc oxide (ZnO) and zinc oxide nanoparticles (ZnONPs) on Escherichia coli . These compounds are commonly used as fertilizers and feed additives and may have unintended consequences on bacteria. We conducted phenotypic and multi-omics analyses of E. coli exposed to sub-lethal concentrations of ZnO and ZnONPs for 40 sub-culturings and 20 sub-culturings with zinc followed by 20 sub-culturings without zinc in an attempt to reverse zinc effects. An extended treatment with ZnO for 40 sub-culturings had the greatest impact leading to bacterial resistance to aminoglycosides, cephalosporins, and sulfonamides while the treatment with ZnONPs for 40 sub-culturings led to the elevated MIC to chloramphenicol only. Cells exposed to these treatments were thicker and had retarded growth in elevated temperatures. Importantly, zinc withdrawal reversed most phenotypic changes. Zinc exposure caused dramatic changes in cell transcripts and proteins with a role in antibiotic response, heat stress, growth regulation, cell shape, and biofilm formation. An extended zinc exposure led to overall major alterations in E. coli biology and resulted in multi-drug resistance. IMPORTANCE A long-term exposure of bacteria to zinc oxide and zinc oxide nanoparticles leads to major alterations in bacterial morphology and physiology. These included biochemical and physiological processes promoting the emergence of strains with multi-drug resistance and virulence traits. After the removal of zinc pressure, bacterial phenotype reversed back to the original state; however, certain changes at the genomic, transcriptomic, and proteomic level remained. Why is this important? The extensive and intensive use of supplements in animal feed effects the intestinal microbiota of livestock and this may negatively impact the health of animals and people. Therefore, it is crucial to understand and monitor the impact of feed supplements on intestinal microorganisms in order to adequately assess and prevent potential health risks.