The Yersinia Yops inhibit invasion of Listeria, Shigella and Edwardsiella but not Salmonella into epithelial cells.
Yersinia virulence is dependent on the expression of plasmid-encoded secreted proteins called Yops. After bacterial adherence to receptors on the mammalian cell membrane, several Yops are transported by a type III secretion pathway into the host cell cytoplasm. Two Yops, YopH and YopE, prevent macrophages from phagocytosing Yersinia by disrupting the host cell cytoskeleton and signal transduction pathways. In contrast to this active inhibition of phagocytosis by Yersinia, other pathogens such as Salmonella, Shigella, Listeria and Edwardsiella actively promote their entry into mammalian cells by binding to specific host surface receptors and exploiting existing cell cytoskeletal and signalling pathways. We have tested whether Yersinia Yops can prevent the uptake of these diverse invasive pathogens. We first infected epithelial cells with Yersinia to permit delivery of Yops and subsequently with an invasive pathogen. We then measured the level of bacterial invasion. Preinfection with Yersinia inhibited invasion of Edwardsiella, Shigella and Listeria, but not Salmonella. Furthermore, we found that either YopE or YopH prevented Listeria invasion, whereas only YopE prevented Edwardsiella and Shigella invasion. We correlated the inhibitory effect of the Yops with the inhibitory action of the cell-signalling inhibitors Wortmannin, LY294002 and NDGA, and concluded that the four invasive pathogenic species enter epithelial cells using at least three distinct host cell pathways. We also speculate that YopE affects the rho pathway.
Stanford University School of Medicine, CA 94305-5124, USA. mecsas@cmgm.stanford.edu
J
J
Mecsas
B
B
Raupach
S
S
Falkow
D000730:Androstadienes / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism*; D004755:Enterobacteriaceae / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology*; D005455:Fluorescent Antibody Technique; D005839:Gentamicins / Q000494:pharmacology; D006801:Humans; D008087:Listeria / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D009637:Masoprocol / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014774:Virulence; D000077191:Wortmannin; D015007:Yersinia / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*
D000730:Androstadienes; D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001427:Bacterial Toxins; D005839:Gentamicins; C063239:yopE protein, Yersinia; D009637:Masoprocol; D000077191:Wortmannin