"Background: The bacterial SOS response is a highly conserved global regulatory system that is activated in response to DNA damage or cellular stress. In this study, we explored the role of the SOS response in the transmission dynamics of the blaNDM -sh-ble gene cassette, a clinically significant determinant of carbapenem resistance. We specifically investigated the expression of SOS-related genes during horizontal gene transfer events involving ISAba125-linked blaNDM-sh-ble gene cassette in V. cholerae strains N16961 and C6709 under selective antibiotic stress environments. Methods: We applied comparative genomics and transcriptomic analysis in  model pathogen Vibrio cholerae. Results: Our findings reveal a distinct correlation between SOS gene expression and the frequency of blaNDM-sh-ble gene cassette transmission in strain N16961. This suggests that the activation of the SOS response enhances the mobilization of resistance genes, likely through upregulation of recombination and transposition enzymes, as well as increased competence genes for natural transformation.  In contrast, strain C6709 exhibited significantly reduced transformation frequency, and this reduction appeared to be independent of SOS gene expression. Interestingly, when exposed to sublethal concentrations of antibiotics, strain C6709 showed a further decline in transformation frequency. This is a particularly notable observation, as sub-inhibitory antibiotic levels have been previously reported to induce the SOS response and enhance AMR genes spread in various bacterial species.  The lack of such an effect in C6709 implies the existence of strain-specific regulatory mechanisms or a differential stress response that suppresses or fails to activate the SOS pathway in the same manner as observed in N16961."