title: A simple model host for identifying Gram-positive virulence factors.
abstract: We demonstrate the use of the nematode Caenorhabditis elegans as a facile and inexpensive model host for several Gram-positive human bacterial pathogens. Enterococcus faecalis, Streptococcus pneumoniae, and Staphylococcus aureus, but not Bacillus subtilis, Enterococcus faecium, or Streptococcus pyogenes, kill adult C. elegans. Focusing our studies on the enterococcal species, we found that both E. faecalis and E. faecium kill C. elegans eggs and hatchlings, although only E. faecalis kills the adults. In the case of adults, a low inoculum of E. faecalis grows to a high titer in the C. elegans intestine, resulting in a persistent infection that cannot be eradicated by prolonged feeding on E. faecium. Interestingly, a high titer of E. faecium also accumulates in the nematode gut, but does not affect the longevity of the worms. Two E. faecalis virulence-related factors that play an important role in mammalian models of infection, fsr, a putative quorum-sensing system, and cytolysin, are also important for nematode killing. We exploit the apparent parallels between Gram-positive infection in simple and more complex organisms by using the nematode to identify an E. faecalis virulence factor, ScrB, which is relevant to mammalian pathogenesis.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Garsin
authors.forename: C D
authors.initials: CD
authors.lastname: Sifri
authors.forename: E
authors.initials: E
authors.lastname: Mylonakis
authors.forename: X
authors.initials: X
authors.lastname: Qin
authors.forename: K V
authors.initials: KV
authors.lastname: Singh
authors.forename: B E
authors.initials: BE
authors.lastname: Murray
authors.forename: S B
authors.initials: SB
authors.lastname: Calderwood
authors.forename: F M
authors.initials: FM
authors.lastname: Ausubel
mesh_terms: D000818:Animals; D001412:Bacillus subtilis; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001430:Bacteriocins; D017173:Caenorhabditis elegans / Q000382:microbiology*; D003603:Cytotoxins / Q000235:genetics / Q000502:physiology*; D004064:Digestive System / Q000382:microbiology; D004195:Disease Models, Animal; D013293:Enterococcus faecalis / Q000254:growth & development / Q000472:pathogenicity*; D016984:Enterococcus faecium; D017353:Gene Deletion; D006094:Gram-Positive Bacteria / Q000472:pathogenicity; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D013211:Staphylococcus aureus / Q000472:pathogenicity; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D013297:Streptococcus pyogenes
chemical_list: D001426:Bacterial Proteins; D001430:Bacteriocins; D003603:Cytotoxins; C409032:FsrB protein, Enterococcus; C065937:aggregation substance, Enterococcus faecalis; C120351:cytolysin, Enterococcus faecalis