Caenorhabditis elegans-based screen identifies Salmonella virulence factors required for conserved host-pathogen interactions.
A Caenorhabditis elegans-Salmonella enterica host-pathogen model was used to identify both novel and previously known S. enterica virulence factors (HilA, HilD, InvH, SptP, RhuM, Spi4-F, PipA, VsdA, RepC, Sb25, RfaL, GmhA, LeuO, CstA, and RecC), including several related to the type III secretion system (TTSS) encoded in Salmonella pathogenicity island 1 (SPI-1). Mutants corresponding to presumptive novel virulence-related genes exhibited diminished ability to invade epithelial cells and/or to induce polymorphonuclear leukocyte migration in a tissue culture model of mammalian enteropathogenesis. When expressed in C. elegans intestinal cells, the S. enterica TTSS-exported effector protein SptP inhibited a conserved p38 MAPK signaling pathway and suppressed the diminished pathogenicity phenotype of an S. enterica sptP mutant. These results show that C. elegans is an attractive model to study the interaction between Salmonella effector proteins and components of the innate immune response, in part because there is a remarkable overlap between Salmonella virulence factors required for human and nematode pathogenesis.
Tenor
Jennifer L
JL
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710 USA.
McCormick
Beth A
BA
Ausubel
Frederick M
FM
Aballay
Alejandro
A
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D017173:Caenorhabditis elegans; D004251:DNA Transposable Elements; D004195:Disease Models, Animal; D004847:Epithelial Cells; D015870:Gene Expression; D044404:Genomic Islands / Q000235:genetics; D007113:Immunity, Innate / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012480:Salmonella Infections / Q000276:immunology / Q000503:physiopathology*; D019779:Salmonella enterica / Q000235:genetics* / Q000472:pathogenicity*; D013696:Temperature; D013997:Time Factors; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics*; D048051:p38 Mitogen-Activated Protein Kinases
D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D037521:Virulence Factors; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases