Garsin, Danielle A.Sifri, Costi D.Mylonakis, EleftheriosQin, XiangSingh, Kavindra V.Murray, Barbara E.Calderwood, Stephen B.Ausubel, Frederick M.2019-10-122001Garsin, D. A., C. D. Sifri, E. Mylonakis, X. Qin, K. V. Singh, B. E. Murray, S. B. Calderwood, and F. M. Ausubel. 2001. “A Simple Model Host for Identifying Gram-Positive Virulence Factors.” Proceedings of the National Academy of Sciences98 (19): 10892–97. doi:10.1073/pnas.191378698.0027-84240744-28311091-6490http://nrs.harvard.edu/urn-3:HUL.InstRepos:41542634We 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, tsr, 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.en-USJournal Article2019-10-1210.1073/pnas.191378698