Aggregation of host endosomes by Salmonella requires SPI2 translocation of SseFG and involves SpvR and the fms-aroE intragenic region

Mol Microbiol. 2000 Sep;37(6):1417-35. doi: 10.1046/j.1365-2958.2000.02092.x.

Abstract

Salmonella-induced aggregation of host endosomal compartments into tubules, termed lgp-tubules, requires sifA and ompR. Lgp-tubules result from Salmonella-directed alteration of the endocytic system and typify the unique intracellular locale where Salmonella replicate. A high-throughput method devised to screen 11 520 MudJ mutants for loss of lgp-tubule formation identified one auxotrophic and nine prototrophic mutants. Molecular characterization identified four new loci required to alter epithelial endocytic structure. Salmonella pathogenicity island 2 (SPI2) is the locus central to the phenotype. A subset of SPI2 effectors is essential: SpiC and SseFG are required, but not SseE. A subset of apparatus proteins is also implicated: SsaJ, L, M, V and P are required. SPI2 was implicated further, as SifA shows similarity with known SPI2 translocation targets, and OmpR regulates SPI2. Another locus lies within the smf-aroE intragenic region. Lgp-tubule formation also involves a locus on the virulence plasmid pSLT. The pSLT-encoded SpvR negatively regulates an unknown repressor of the phenotype located on pSLT. Finally, disruption of carB leads to multiple auxotrophy that prevents lgp-tubule formation. This study demonstrates that lgp-tubule formation is a virulence mechanism that underlies the selective disruption of host endocytic trafficking and is associated with the formation of a replication-permissive locale.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism*
  • Cefotaxime / pharmacology
  • Cell Line
  • DNA Transposable Elements
  • Dogs
  • Endosomes / microbiology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / microbiology*
  • Epithelial Cells / ultrastructure
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Bacterial
  • Genetic Techniques
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Protein Transport
  • Salmonella / drug effects
  • Salmonella / genetics
  • Salmonella / pathogenicity*
  • Sequence Homology, Amino Acid
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription, Genetic
  • Vacuoles / microbiology
  • Vacuoles / ultrastructure
  • Virulence / genetics

Substances

  • Bacterial Proteins
  • DNA Transposable Elements
  • Trans-Activators
  • osmolarity response regulator proteins
  • Cefotaxime