Updated project metadata. Horizontally acquired genetic elements (HGEs) plays a major for determination of virulence, antimicrobial resistance, adaptation and evolution in pathogenic bacteria. Conserved integrative mobile genetic elements (MGEs) of Vibrio cholerae contribute in the disease development, antimicrobial resistance and metabolic functions. To understand the dynamics of integrative MGEs and cross talk between MGEs and core genome, engineered genome of V. cholerae was monitored in the presence and absence of horizontally acquired genetic elements. Deletion of more than 250 revealed that CTX contributes to the essentiality of SOS response master regulator LexA in V. cholerae. Also, he core genome encoded RecA helps CTX to bypass the host immunity and replicate in the host cell in the presence of similar prophage in the host chromosome. Finally, our multiomics data reveal importance of MGEs in modulating the level of cellular proteome and metabolome in V. cholerae. This study for the first time engineered the genome of V. cholerae strains to eliminate all the GIs, ICE and prophages from their genome and revealed new interactions between core and acquired genomes. The engineered strain could be a potential candidate for understanding evolution of cholera pathogen and development of therapeutics.