Non-growth inhibitory doses of dimethyl sulfoxide alter gene expression and epigenetic pattern of bacteria

Although dimethyl sulfoxide (DMSO) is a widely used solvent in scientific research, drug screening settings, and biomedical applications, its solvent (vehicle) effects on biological processes are overlooked. Using Escherichia coli as a model, we aimed to investigate and evaluate the effects of low-dose DMSO-driven changes in bacterial cells in a comprehensive and multifaceted manner by combining Fourier transform infrared spectroscopy analyses, analytical cell-biology approaches, and high-throughput sequencing. Here, we show that the non-toxic (1.0 and 2.5%, v/v) DMSO doses reduce the cellular levels of reactive oxygen species, change the cellular nucleic acid content and DNA topology, affect the global 5-methylcytosine pattern of the genome, and modulate gene transcription. These results indicate that even at non-toxic concentrations, DMSO is not inert: it can alter validity by changing or masking the assessed activity of the analyte. Besides, this manuscript does not only highlight that the low, non-toxic solvent doses of DMSO impinge on biological processes, including genome structure and function, but also, the high-throughput sequence data obtained during the study offer a platform for future research to elucidate the mechanism of epigenetically regulated genes in bacteria. KEY POINTS: • A clear-cut differentiation between the low-dose DMSO-treated and -untreated bacteria by PCA and LDA. • Drastic alterations in the DNA topology and nucleic acids of DMSO-treated bacteria. • Changes in transcriptome and epigenetic signatures with the low-dose DMSO.