Genome-wide RNAi screen for host factors required for intracellular bacterial infection

Science. 2005 Aug 19;309(5738):1248-51. doi: 10.1126/science.1116008. Epub 2005 Jul 14.

Abstract

Most studies of host-pathogen interactions have focused on pathogen-specific virulence determinants. Here, we report a genome-wide RNA interference screen to identify host factors required for intracellular bacterial pathogenesis. Using Drosophila cells and the cytosolic pathogen Listeria monocytogenes, we identified 305 double-stranded RNAs targeting a wide range of cellular functions that altered L. monocytogenes infection. Comparison to a similar screen with Mycobacterium fortuitum, a vacuolar pathogen, identified host factors that may play a general role in intracellular pathogenesis and factors that specifically affect access to the cytosol by L. monocytogenes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Line
  • Cytoskeleton / metabolism
  • Cytosol / microbiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Drosophila melanogaster / microbiology*
  • Genes, Insect*
  • Genome
  • Green Fluorescent Proteins / metabolism
  • Listeria monocytogenes / growth & development
  • Listeria monocytogenes / pathogenicity
  • Listeria monocytogenes / physiology*
  • Macrophages / microbiology*
  • Macrophages / physiology
  • Mycobacterium fortuitum / growth & development
  • Mycobacterium fortuitum / pathogenicity
  • Mycobacterium fortuitum / physiology
  • Phenotype
  • RNA Interference*
  • RNA Processing, Post-Transcriptional
  • RNA, Double-Stranded / pharmacology
  • Signal Transduction / genetics
  • Vacuoles / microbiology
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism

Substances

  • Drosophila Proteins
  • RNA, Double-Stranded
  • Vesicular Transport Proteins
  • Green Fluorescent Proteins