Pangenome and Transcriptomic Analysis Revealed Distinct Virulence Genes Profiles and Infection Responses in Shigella Sonnei and Shigella Flexneri

Shigellosis, a major cause of diarrheal death, is predominantly caused by Shigella flexneri and Shigella sonnei. Notably, S. sonnei has begun to overtake S. flexneri in incidence worldwide. We conducted a comparative pangenome and transcriptomic analysis of these two species using the well-established model Caenorhabditis elegans as an infection model to explore this shift. Pangenome analysis of 46 S. sonnei and 111 S. flexneri strains revealed that S. sonnei has more core genes (44%) than S. flexneri (13.6%). Additionally, S. sonnei, but not S. flexneri, has core virulence genes. The transcriptomic study during C. elegans infection showed that S. sonnei significantly upregulates the ferric enterobactin outer membrane transporter (fepA) and other metabolic processes (sulfur, thiamine and arginine). In contrast, S. flexneri upregulates regulatory genes involved in biofilm formation, transcription, cellular processes, and cell communication. These findings suggest that S. sonneis ability to upregulate specific genes, including fepA, may confer a competitive advantage over S. flexneri. These findings provide a comprehensive understanding of the genetic and functional adaptations that may contribute to the global epidemiological shift from S. flexneri to S. sonnei, underscoring the need for further research into the mechanisms driving S. sonneis increased virulence and adaptability.