Synthetic bottom-up approach reveals the complex interplay of Shigella effectors in regulation of epithelial cell death

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Abstract
Significance: The virulence of numerous bacterial pathogens is dependent on nanomachines that inject tens of proteins (effectors) into host cells. Effectors are often functionally redundant or act in an additive manner to usurp cellular processes, limiting their characterization via traditional top-down loss-of-function assays. To overcome this issue, we developed an innovative synthetic bottom-up platform to conduct gain-of-function screens. These screens identified previously missed Shigella effectors that inhibit induced epithelial cell death, an important arm of the host innate immune system triggered in response to invading pathogens. Our studies provide new mechanistic insight into the sophisticated strategies by which Shigella effectors interact with the host to enable this pathogen to establish a replicative niche within the cytosol of infected epithelial cells.
Funding Information
  • HHS | NIH | National Institute of Allergy and Infectious Diseases (R01 AI064285)

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