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Quantitative Yeast Genetic Interaction Profiling of Bacterial Effector Proteins Uncovers a Role for the Human Retromer in Salmonella Infection.

Cell systems | 2018

Intracellular bacterial pathogens secrete a repertoire of effector proteins into host cells that are required to hijack cellular pathways and cause disease. Despite decades of research, the molecular functions of most bacterial effectors remain unclear. To address this gap, we generated quantitative genetic interaction profiles between 36 validated and putative effectors from three evolutionarily divergent human bacterial pathogens and 4,190 yeast deletion strains. Correlating effector-generated profiles with those of yeast mutants, we recapitulated known biology for several effectors with remarkable specificity and predicted previously unknown functions for others. Biochemical and functional validation in human cells revealed a role for an uncharacterized component of the Salmonella SPI-2 translocon, SseC, in regulating maintenance of the Salmonella vacuole through interactions with components of the host retromer complex. These results exhibit the power of genetic interaction profiling to discover and dissect complex biology at the host-pathogen interface.

Pubmed ID: 30077634 RIS Download

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI145287
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI120694
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI122747
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI090142
  • Agency: NIAID NIH HHS, United States
    Id: R21 AI123753
  • Agency: NICHD NIH HHS, United States
    Id: R01 HD084339
  • Agency: NCI NIH HHS, United States
    Id: U54 CA209891
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM084279
  • Agency: NIAID NIH HHS, United States
    Id: F32 AI116410
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI125512

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SGD (tool)

RRID:SCR_004694

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