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<p>Studying human-adapted pathogens like <i>Shigella flexneri</i> is challenging because animal models poorly mimic human physiology and suffer from infection bottlenecks. We developed a scalable workflow combining human organoid infections with Transposon Insertion Sequencing to map disruptions of <i>Shigella</i> genes affecting colonization. Systematic optimization of mutant library size, infection and culture conditions along with Bayesian modeling enabled genome-wide identification of colonization factors.</p>

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Skalierbares Darmorganoidmodell enthüllt humanpathogene Infektionsfaktoren

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月22日

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  • Laura Jenniches,
  • Maria Letizia Di Martino,
  • Mikael E. Sellin,
  • Lars Barquist

摘要

Studying human-adapted pathogens like Shigella flexneri is challenging because animal models poorly mimic human physiology and suffer from infection bottlenecks. We developed a scalable workflow combining human organoid infections with Transposon Insertion Sequencing to map disruptions of Shigella genes affecting colonization. Systematic optimization of mutant library size, infection and culture conditions along with Bayesian modeling enabled genome-wide identification of colonization factors.