Title | A simple model host for identifying Gram-positive virulence factors. |
Publication Type | Journal Article |
Year of Publication | 2001 |
Authors | Garsin, DA, Sifri, CD, Mylonakis, E, Qin, X, Singh, KV, Murray, BE, Calderwood, SB, Ausubel, FM |
Journal | Proc Natl Acad Sci U S A |
Volume | 98 |
Issue | 19 |
Pagination | 10892-7 |
Date Published | 2001 Sep 11 |
ISSN | 0027-8424 |
Keywords | Animals, 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. |
DOI | 10.1073/pnas.191378698 |
Alternate Journal | Proc Natl Acad Sci U S A |
PubMed ID | 11535834 |
PubMed Central ID | PMC58570 |
Grant List | R01 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 |
A simple model host for identifying Gram-positive virulence factors.
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