title: The Fsr quorum-sensing system of Enterococcus faecalis modulates surface display of the collagen-binding MSCRAMM Ace through regulation of gelE.
abstract: Ace, a known virulence factor and the first identified microbial surface component recognizing adhesive matrix molecule (MSCRAMM) of Enterococcus faecalisis associated with host cell adherence and endocarditis. The Fsr quorum-sensing system of E. faecalis, a two-component signal transduction system, has also been repeatedly linked to virulence in E. faecalis, due in part to the transcriptional induction of an extracellular metalloprotease, gelatinase (GelE). In this study, we discovered that disruption of the Fsr pathway significantly increased the levels of Ace on the cell surface in the latter phases of growth. Furthermore, we observed that, in addition to fsrB mutants, other strains identified as deficient in GelE activity also demonstrated a similar phenotype. Additional experiments demonstrated the GelE-dependent cleavage of Ace from the surface of E. faecalis, confirming that GelE specifically reduces Ace cell surface display. In addition, disruption of the Fsr system or GelE expression significantly improved the ability of E. faecalis to adhere to collagen, which is consistent with higher levels of Ace on the E. faecalis surface. These results demonstrate that the display of Ace is mediated by quorum sensing through the action of GelE, providing insight into the complicated world of Gram-positive pathogen adhesion and colonization.
authors.affiliation: Center for Immunology and Autoimmune Diseases, Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Pinkston
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.forename: Daniel
authors.initials: D
authors.lastname: Diaz-Garcia
authors.forename: Jouko
authors.initials: J
authors.lastname: Sillanpää
authors.forename: Sreedhar R
authors.initials: SR
authors.lastname: Nallapareddy
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Murray
authors.forename: Barrett R
authors.initials: BR
authors.lastname: Harvey
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D013293:Enterococcus faecalis / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D005434:Flow Cytometry; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005810:Multigene Family; D010641:Phenotype; D053038:Quorum Sensing / Q000235:genetics*; D017384:Sequence Deletion; D015398:Signal Transduction
chemical_list: C121675:Ace protein, Enterococcus; D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; C409031:FsrA protein, Enterococcus faecalis; D018093:Gelatinases