The world is currently going through seventh wave of cholera pandemics, which are predominantly caused by the toxigenic strains of Vibrio cholerae. These strains of V. cholerae are believed to be evolved through a series of horizontal gene transfer (HGT) events mediated by mobile genetic elements (MGE), which often harbor virulence and antimicrobial resistance (AMR) genes. While the diversity of these genes are well-studied, the defense systems that allow V. cholerae to resist MGE invasion remain poorly understood. To address this knowledge gap, we systematically identified anti-phage islands, prophages, and AMR genes in 1740 V. cholerae NCBI RefSeq genomes using bioinformatic tools, including Defense Finder, VirSorter, and ABRicate. Our analysis revealed novel insights into the diversity and distribution of these elements within V. cholerae genomes. We observed a positive correlation between the number of AMR and anti-phage island genes, suggesting a potential co-transfer

mechanism. In contrast, a negative correlation was found between prophage and anti-phage island genes, indicating a competitive relationship. Furthermore, our analysis unveiled associations between specific anti-phage island and AMR genes, which may play a crucial role in the dissemination of AMR genes within V. cholerae populations. This study sheds light on the complex interplay between AMR, prophage, and anti-phage defense systems in V. cholerae. These findings have significant implications for understanding the evolutionary dynamics of this pathogen and may inform the development of novel strategies to combat cholera.