title: Drosophila host model reveals new enterococcus faecalis quorum-sensing associated virulence factors.
abstract: Enterococcus faecalis V583 is a vancomycin-resistant clinical isolate which belongs to the hospital-adapted clade, CC2. This strain harbours several factors that have been associated with virulence, including the fsr quorum-sensing regulatory system that is known to control the expression of GelE and SprE proteases. To discriminate between genes directly regulated by Fsr, and those indirectly regulated as the result of protease expression or activity, we compared gene expression in isogenic mutants of V583 variously defective in either Fsr quorum sensing or protease expression. Quorum sensing was artificially induced by addition of the quorum signal, GBAP, exogenously in a controlled manner. The Fsr regulon was found to be restricted to five genes, gelE, sprE, ef1097, ef1351 and ef1352. Twelve additional genes were found to be dependent on the presence of GBAP-induced proteases. Induction of GelE and SprE by GBAP via Fsr resulted in accumulation of mRNA encoding lrgAB, and this induction was found to be lytRS dependent. Drosophila infection was used to discern varying levels of toxicity stemming from mutations in the fsr quorum regulatory system and the genes that it regulates, highlighting the contribution of LrgAB and bacteriocin EF1097 to infection toxicity. A contribution of SprE to infection toxicity was also detected. This work brought to light new players in E. faecalis success as a pathogen and paves the way for future studies on host tolerance mechanisms to infections caused by this important nosocomial pathogen.
authors.affiliation: ITQB Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Neuza
authors.initials: N
authors.lastname: Teixeira
authors.forename: Sriram
authors.initials: S
authors.lastname: Varahan
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gorman
authors.forename: Kelli L
authors.initials: KL
authors.lastname: Palmer
authors.forename: Anna
authors.initials: A
authors.lastname: Zaidman-Remy
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yokohata
authors.forename: Jiro
authors.initials: J
authors.lastname: Nakayama
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Hancock
authors.forename: António
authors.initials: A
authors.lastname: Jacinto
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gilmore
authors.forename: Maria
authors.initials: M
authors.lastname: de Fátima Silva Lopes
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000382:microbiology*; D013293:Enterococcus faecalis / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D054884:Host-Pathogen Interactions; D008297:Male; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D053038:Quorum Sensing / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
chemical_list: C409033:AgrCfs protein, Enterococcus faecalis; D001426:Bacterial Proteins; C409031:FsrA protein, Enterococcus faecalis; C409032:FsrB protein, Enterococcus; D037521:Virulence Factors