title: Virulence effect of Enterococcus faecalis protease genes and the quorum-sensing locus fsr in Caenorhabditis elegans and mice.
abstract: The expression of two Enterococcus faecalis extracellular virulence-related proteins, gelatinase (GelE) and serine protease (SprE), has been shown to be positively regulated by the fsr quorum-sensing system. We recently developed a novel system for studying E. faecalis pathogenicity that involves killing of the nematode worm Caenorhabditis elegans and showed that an E. faecalis fsrB mutant (strain TX5266) exhibited attenuated killing. We explore here the role of the fsr/gelE-sprE locus in pathogenicity by comparing results obtained in the nematode system with a mouse peritonitis model of E. faecalis infection. Insertion mutants of fsrA (TX5240) and fsrC (TX5242), like fsrB (TX5266), were attenuated in their ability to kill C. elegans. A deletion mutant of gelE (TX5264) and an insertion mutant of sprE (TX5243) were also attenuated in C. elegans killing, although to a lesser extent than the fsr mutants. Complementation of fsrB (TX5266) with a 6-kb fragment containing the entire fsr locus restored virulence in both the nematode and the mouse peritonitis models. The fsr mutants were not impaired in their ability to colonize the nematode intestine. These data show that extracellular proteases and the quorum-sensing fsr system are important for E. faecalis virulence in two highly divergent hosts: nematodes and mice.
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Costi D
authors.initials: CD
authors.lastname: Sifri
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
authors.forename: Kavindra V
authors.initials: KV
authors.lastname: Singh
authors.forename: Xiang
authors.initials: X
authors.lastname: Qin
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Garsin
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Murray
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Ausubel
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Calderwood
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D017173:Caenorhabditis elegans; D004268:DNA-Binding Proteins; D013293:Enterococcus faecalis / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity*; D029968:Escherichia coli Proteins; D005260:Female; D018093:Gelatinases / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D051379:Mice; D008813:Mice, Inbred ICR; D016254:Mutagenesis, Insertional; D017384:Sequence Deletion; D014157:Transcription Factors; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C409032:FsrB protein, Enterococcus; D014157:Transcription Factors; C098923:rssB protein, E coli; D018093:Gelatinases