In this study, the molecular profile changes leading to the adaptation of bacteria to survive and grow at inhibitory silver concentration were explored. The profile obtained through infrared (IR)-based measurements indicated extensive changes in all biomolecular components, which were supported by chemometric techniques. The changes in biomolecular profile were prominent, including nucleic acids. The changes in nucleic acid region (1350-950 cm(-1)) were encountered as a clue for conformational change in DNA. Further analysis of DNA by IR spectroscopy revealed changes in the backbone and sugar conformations. Moreover, Enzyme-Linked Immunosorbent Assay-based measurements of DNA methylation levels were performed to see if epigenetic mechanisms are in operation during bacterial adaptation to this environmental challenge. The results indicated a notable demethylation in Escherichia coli and methylation in Staphylococcus aureus likely to be associated with their elaborate adaptation process to sustain survival and growth.