Importance of the envelope in Escherichia coli resistance to lithium

The increasing use of lithium (Li) in emerging technologies has prompted concerns about its effects on living microorganisms. To enhance our understanding of the bacterial cytotoxicity of Li, we conducted a deletomic analysis using the bacterial model Escherichia coli. A screen of 3,985 knockout mutants under Li stress highlighted 27 Li-sensitive and 15 Li-resistant mutants. The synthesis of peptidoglycan and the capsule, along with the secretion of colanic acid, contributed to resistance to Li. Ribosomes and the stringent response also seem to play a role in mitigating Li cytotoxicity. A cross-metal comparison revealed that the Li-sensitive phenotype of the mutants was shared with Ca, whereas the resistant phenotype was shared with Mg, Na and K. Moreover, this allowed the identification of ΔacrA as a Li sensitivity-specific mutant. AcrA is a subunit of the AcrAB-TolC efflux pump, which is responsible for the efflux of various xenobiotics. We demonstrate that ΔacrB-ΔtolC accumulates approximately 1.5 times more Li than the WT, indicating that this pump could also facilitate the efflux of Li. This study offers a more comprehensive insight into the mechanisms involved in the Li response in E. coli.