Unveiling the strategies of bacterial adaptation to stress constitute a challenging area of research. The understanding of mechanisms governing emergence of resistance to antimicrobials is of particular importance regarding the increasing threat of antibiotic resistance on public health worldwide. In the last decades, the fast democratization of sequencing technologies along with the development of dedicated bioinformatical tools to process data offered new opportunities to characterize genomic variations underlying bacterial adaptation. Thereby, research teams have now the possibility to dive deeper in the deciphering of bacterial adaptive mechanisms through the identification of specific genetic targets mediating survival to stress. In this chapter, we proposed a step-by-step bioinformatical pipeline enabling the identification of mutational events underlying biocidal stress adaptation associated with antimicrobial resistance development using Escherichia marmotae as an illustrative model.