Quantitative Yeast Genetic Interaction Profiling of Bacterial Effector Proteins Uncovers a Role for the Human Retromer in Salmonella Infection | Academic Article individual record
abstract

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.

author list (cited authors)
Patrick, K. L., Wojcechowskyj, J. A., Bell, S. L., Riba, M. N., Jing, T., Talmage, S., ... Watson, R. O.
publication date
2018
publisher
Elsevier bv Publisher
published in
Cell systems Journal
keywords
  • Bacterial Proteins
  • Animals
  • High-Throughput Screening Assays
  • Genetic Interaction Profile
  • Signal Transduction
  • Retromer Complex
  • Salmonella Infections
  • Intracellular Bacteria
  • Host-Pathogen Interactions
  • Microorganisms, Genetically-modified
  • Host-pathogen Interaction
  • Hela Cells
  • Gene Regulatory Networks
  • Humans
  • E-map
  • Salmonella Enterica Serovar Typhimurium
  • Bacterial Effector Protein
  • Salmonella Typhi
  • Yeasts
  • Multiprotein Complexes
  • Mice
  • Mutation
altmetric score

6.0

citation count

6