Department of Biological Sciences, Birla Institute of Technology & Science (BITS), Pilani, Rajasthan, India.
School of Biological Sciences, University of Southampton, Southampton, United Kingdom.
PLoS Biol. 2024 Aug 7;22(8):e3002746. doi: 10.1371/journal.pbio.3002746. eCollection 2024 Aug.
Understanding the dynamic evolution of Salmonella is vital for effective bacterial infection management. This study explores the role of the flexible genome, organised in regions of genomic plasticity (RGP), in shaping the pathogenicity of Salmonella lineages. Through comprehensive genomic analysis of 12,244 Salmonella 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 Salmonella 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 Salmonella lineages. Overall, this study provides a comprehensive blueprint of the pathogenicity potential of Salmonella. 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.
了解沙门氏菌的动态进化对于有效管理细菌感染至关重要。本研究探讨了灵活基因组在塑造沙门氏菌谱系致病性方面的作用，该基因组组织在基因组可塑性区域（RGP）中。通过对涵盖 2 个种、6 个亚种和 46 个血清型的 12244 株沙门氏菌 spp.基因组进行全面的基因组分析，我们揭示了与致病性相关的基因簇整合到 RGP 中的独特模式，挑战了传统的基因分布观点。这些 RGP 对特定基因组位置表现出明显的偏好，而这些位置在沙门氏菌谱系中的存在或缺失极大地影响了菌株的致病性。RGP 偏好受到整合位置周围保守侧翼基因的指导，暗示它们参与了调控网络和与整合基因簇的功能协同作用。此外，我们强调了质粒和原噬菌体对多种沙门氏菌谱系致病性的多方面贡献。总体而言，本研究提供了沙门氏菌致病性潜力的综合蓝图。这种独特的见解确定了非致病性谱系中可能携带致病性基因的基因组位置，为预测未来的适应性和开发针对新兴人类致病性菌株的靶向策略提供了基础。
