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This study explores the role of the flexible genome, organised in regions of genomic plasticity (RGP), in shaping the pathogenicity of\n                    <jats:italic>Salmonella<\/jats:italic>\n                    lineages. Through comprehensive genomic analysis of 12,244\n                    <jats:italic>Salmonella<\/jats:italic>\n                    spp. genomes covering 2 species, 6 subspecies, and 46 serovars, we uncover distinct integration patterns of pathogenicity-related gene clusters into RGP, challenging traditional views of gene distribution. These RGP exhibit distinct preferences for specific genomic spots, and the presence or absence of such spots across\n                    <jats:italic>Salmonella<\/jats:italic>\n                    lineages profoundly shapes strain pathogenicity. RGP preferences are guided by conserved flanking genes surrounding integration spots, implicating their involvement in regulatory networks and functional synergies with integrated gene clusters. Additionally, we emphasise the multifaceted contributions of plasmids and prophages to the pathogenicity of diverse\n                    <jats:italic>Salmonella<\/jats:italic>\n                    lineages. Overall, this study provides a comprehensive blueprint of the pathogenicity potential of\n                    <jats:italic>Salmonella<\/jats:italic>\n                    . This unique insight identifies genomic spots in nonpathogenic lineages that hold the potential for harbouring pathogenicity genes, providing a foundation for predicting future adaptations and developing targeted strategies against emerging human pathogenic strains.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3002746","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T13:24:57Z","timestamp":1723037097000},"page":"e3002746","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["Comprehensive blueprint of Salmonella genomic plasticity identifies hotspots for pathogenicity genes"],"prefix":"10.1371","volume":"22","author":[{"given":"Simran","family":"Krishnakant 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