A simple model host for identifying Gram-positive virulence factors.

TitleA simple model host for identifying Gram-positive virulence factors.
Publication TypeJournal Article
Year of Publication2001
AuthorsGarsin, DA, Sifri, CD, Mylonakis, E, Qin, X, Singh, KV, Murray, BE, Calderwood, SB, Ausubel, FM
JournalProc Natl Acad Sci U S A
Volume98
Issue19
Pagination10892-7
Date Published2001 Sep 11
ISSN0027-8424
KeywordsAnimals, Bacillus subtilis, Bacterial Proteins, Bacteriocins, Caenorhabditis elegans, Cytotoxins, Digestive System, Disease Models, Animal, Enterococcus faecalis, Enterococcus faecium, Gene Deletion, Gram-Positive Bacteria, Humans, Mice, Mice, Inbred ICR, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes
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.

DOI10.1073/pnas.191378698
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID11535834
PubMed Central IDPMC58570
Grant ListR01 AI042399 / AI / NIAID NIH HHS / United States
R56 AI042399 / AI / NIAID NIH HHS / United States
R01 AI047923 / AI / NIAID NIH HHS / United States
AI42399 / AI / NIAID NIH HHS / United States
AI47923 / AI / NIAID NIH HHS / United States
R37 AI047923 / AI / NIAID NIH HHS / United States