Pangenome and Transcriptomic Analysis Revealed Distinct Virulence Genes Profiles and Infection Responses inShigella SonneiandShigella Flexneri

Abstract

AbstractShigellosis, a major cause of diarrheal death, is predominantly caused byShigella flexneriandShigella sonnei. Notably,S. sonneihas begun to overtakeS. flexneriin incidence worldwide. We conducted a comparative pangenome and transcriptomic analysis of these two species using the well-established modelCaenorhabditis elegansas an infection model to explore this shift. Pangenome analysis of 46S. sonneiand 111S. flexneristrains revealed thatS. sonneihas more core genes (44%) thanS. flexneri(13.6%). Additionally,S. sonnei,but notS. flexneri,has core virulence genes. The transcriptomic study duringC. elegansinfection showed thatS. sonneisignificantly upregulates the ferric enterobactin outer membrane transporter (fepA) and other metabolic processes (sulfur, thiamine and arginine). In contrast,S. flexneriupregulates regulatory genes involved in biofilm formation, transcription, cellular processes, and cell communication. These findings suggest thatS. sonnei’s ability to upregulate specific genes, includingfepA,may confer a competitive advantage overS. flexneri. These findings provide a comprehensive understanding of the genetic and functional adaptations that may contribute to the global epidemiological shift fromS. flexneritoS. sonnei, underscoring the need for further research into the mechanisms drivingS. sonnei’s increased virulence and adaptability.