Paralysis and killing of Caenorhabditis elegans by enteropathogenic Escherichia coli requires the bacterial tryptophanase gene

摘要: Pathogenic Escherichia coli, including enteropathogenic E. coli (EPEC), enterohaemorrhagic (EHEC), enteroinvasive (EIEC) and enterotoxigenic (ETEC) are major causes of food water-borne disease. We have developed a genetically tractable model pathogenic virulence based on our observation that these bacteria paralyse kill the nematode Caenorhabditis elegans. Paralysis killing C. elegans by EPEC did not require direct contact, suggesting secreted toxin mediates effect. Virulence against required tryptophan bacterial tryptophanase, enzyme catalysing production indole other molecules from tryptophan. Thus, lack in growth media or deletion tryptophanase gene failed to While known metabolites complement an mutant when presented extracellularly, complementation was achieved with itself expressed either within pathogen cocultured K12 strains. unknown metabolite derived commensal non-pathogenic strains, appears directly indirectly regulate EPEC. strains containing mutations locus enterocyte effacement (LEE), pathogenicity island for humans, also displayed attenuated capacity nematodes. Furthermore, activity full activation LEE1 promoter, efficient formation actin-filled membranous protrusions (attaching effacing lesions) form surface mammalian epithelial cells following attachment which depends LEE genes. Finally, several genes, hif-1 egl-9, rendered less susceptible mutated, their involvement mediating effects. Other genes sek-1, mek-1, mev-1, pgp-1,3 vhl-1, more effects protecting worms. Moreover we found controlling lifespan (daf-2, age-1 daf-16), mediate susceptibility Together, data suggest this elegans/EPEC system will be valuable elucidating novel factors relevant human disease infection host.