Aggregation of host endosomes by Salmonella requires SPI2 translocation of SseFG and involves SpvR and the fms-aroE intragenic region.
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.
Guy
R L
RL
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405-0068, USA.
Gonias
L A
LA
Stein
M A
MA
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D002439:Cefotaxime / Q000494:pharmacology; D002460:Cell Line; D004251:DNA Transposable Elements; D004285:Dogs; D011992:Endosomes / Q000382:microbiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology* / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D015964:Gene Expression Regulation, Bacterial; D005821:Genetic Techniques; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D021381:Protein Transport; D012475:Salmonella / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014617:Vacuoles / Q000382:microbiology / Q000648:ultrastructure; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D015534:Trans-Activators; C112177:osmolarity response regulator proteins; D002439:Cefotaxime