Genome-wide analysis exploring mechanisms used by <i>Shigella sonnei</i> to survive long-term nutrient starvation

Understanding why <i>Shigella sonnei</i> has a higher prevalence than <i>Shigella flexneri</i> as a country undergoes economic growth is an important challenge in <i>Shigella</i> research. The investigation of their biological and genetic differences is key to tackling the impact of the disease. We discovered that <i>S. sonnei</i> resists nutrient deprivation better than <i>S. flexneri</i>, suggesting a better adaptation to an extracellular lifestyle and a greater preservation of metabolic capabilities. Using a genome-wide transposon sequencing approach, we uncovered the key pathways behind the survival of <i>S. sonnei</i> facing nutrient starvation, which include ATP, nucleotide, and amino acid synthesis as well as maintenance of cell envelope integrity. Comparative analysis between <i>S. sonnei</i> and <i>S. flexneri</i> did not identify an individual gene responsible for the differing survival and may reflect a multifactorial difference. Our data provide a genome-wide basis for understanding how <i>S. sonnei</i> is adapted to nutrient-deprived settings, which may be advantageous in the gut lumen and for environmental survival, potentially contributing to its dominance in high-income countries.