Présenté par Maria Letizia DI MARTINO (Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden)
Invitée par Zeynep BAHARGOLU
Shigella is a major human pathogen that invades and disseminates within the intestinal epithelium, causing bacillary dysentery. Its virulence gene expression is tightly regulated, enabling efficient colonization of the intestinal mucosa. To dissect these regulatory mechanisms in a setting that better reflects human tissue biology, we combined large‑scale infections of human intestinal epithelial organoids with transposon sequencing and computational modelling. This integrative approach generated the most comprehensive map to date of Shigella colonization determinants, identifying more than 100 chromosomal genes essential for infection of the human gut epithelium.
Our work uncovered two previously unreported mechanisms of virulence regulation in Shigella. First, we found that the tRNA‑modifying enzymes MnmE/G together with differential codon usage define a global post‑transcriptional program that modulates virulence gene expression. Second, we identified the chromosomal gene pcnB as a key enhancer of epithelial colonization: by sustaining optimal replication of the Shigella virulence plasmid, pcnB boosts virulence gene expression and strengthens the pathogen’s ability to establish infection.
Together, these findings reveal how coordinated regulatory circuits regulate virulence gene expression to support Shigella successful infection of the human intestinal epithelium.