title: AhrC and Eep are biofilm infection-associated virulence factors in Enterococcus faecalis.
abstract: Enterococcus faecalis is part of the human intestinal microbiome and is a prominent cause of health care-associated infections. The pathogenesis of many E. faecalis infections, including endocarditis and catheter-associated urinary tract infection (CAUTI), is related to the ability of clinical isolates to form biofilms. To identify chromosomal genetic determinants responsible for E. faecalis biofilm-mediated infection, we used a rabbit model of endocarditis to test strains with transposon insertions or in-frame deletions in biofilm-associated loci: ahrC, argR, atlA, opuBC, pyrC, recN, and sepF. Only the ahrC mutant was significantly attenuated in endocarditis. We demonstrate that the transcriptional regulator AhrC and the protease Eep, which we showed previously to be an endocarditis virulence factor, are also required for full virulence in murine CAUTI. Therefore, AhrC and Eep can be classified as enterococcal biofilm-associated virulence factors. Loss of ahrC caused defects in early attachment and accumulation of biofilm biomass. Characterization of ahrC transcription revealed that the temporal expression of this locus observed in wild-type cells promotes initiation of early biofilm formation and the establishment of endocarditis. This is the first report of AhrC serving as a virulence factor in any bacterial species.
authors: Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA. fran0616@umn.edu
authors: Kristi L
authors: KL
authors: Frank
authors: Pascale S
authors: PS
authors: Guiton
authors: Aaron M T
authors: AM
authors: Barnes
authors: Dawn A
authors: DA
authors: Manias
authors: Olivia N
authors: ON
authors: Chuang-Smith
authors: Petra L
authors: PL
authors: Kohler
authors: Adam R
authors: AR
authors: Spaulding
authors: Scott J
authors: SJ
authors: Hultgren
authors: Patrick M
authors: PM
authors: Schlievert
authors: Gary M
authors: GM
authors: Dunny
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D018441:Biofilms; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000382:microbiology*; D013293:Enterococcus faecalis / Q000472:pathogenicity*; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011817:Rabbits; D014157:Transcription Factors / Q000502:physiology*; D037521:Virulence Factors / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; C121786:Eep protein, Enterococcus faecalis; D008565:Membrane Proteins; D014157:Transcription Factors; D037521:Virulence Factors