A scalable gut epithelial organoid model reveals the genome-wide colonization landscape of a human-adapted pathogen.

ABSTRACT: Studying the pathogenesis of human-adapted microorganisms is challenging, since small animal models often fail to recapitulate human physiology. Hence, the comprehensive genetic and regulatory circuits driving the infection process of principal human pathogens such as Shigella flexneri remain to be defined. We combined large-scale Shigella infections of enteroids and colonoids with transposon-directed insertion sequencing and Bayesian statistical modeling to address infection bottlenecks, thereby establishing the comprehensive genome-wide map of Shigella genes required to infect human intestinal epithelium. This revealed the Shigella virulence effectors essential for epithelial cell colonization across geometries and intestinal segments, identified over 100 chromosomal genes involved in th

SUBMITTER: Di Martino ML 

PROVIDER: S-EPMC12283395 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature