title: Genome-wide Screening Identifies Phosphotransferase System Permease BepA to Be Involved in Enterococcus faecium Endocarditis and Biofilm Formation.
abstract: Enterococcus faecium is a common cause of nosocomial infections, of which infective endocarditis is associated with substantial mortality. In this study, we used a microarray-based transposon mapping (M-TraM) approach to evaluate a rat endocarditis model and identified a gene, originally annotated as "fruA" and renamed "bepA," putatively encoding a carbohydrate phosphotransferase system (PTS) permease (biofilm and endocarditis-associated permease A [BepA]), as important in infective endocarditis. This gene is highly enriched in E. faecium clinical isolates and absent in commensal isolates that are not associated with infection. Confirmation of the phenotype was established in a competition experiment of wild-type and a markerless bepA mutant in a rat endocarditis model. In addition, deletion of bepA impaired biofilm formation in vitro in the presence of 100% human serum and metabolism of β-methyl-D-glucoside. β-glucoside metabolism has been linked to the metabolism of glycosaminoglycans that are exposed on injured heart valves, where bacteria attach and form vegetations. Therefore, we propose that the PTS permease BepA is directly implicated in E. faecium pathogenesis.
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, The Netherlands.
authors.forename: Fernanda L
authors.initials: FL
authors.lastname: Paganelli
authors.affiliation: Division of Pediatric Infectious Diseases, Hauner Children's Hospital, Ludwigs-Maximilian Universität München Center for Infectious Disease and Travel Medicine, University Medical Center Freiburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Huebner
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases Center for the Study of Emerging and Re-emerging Pathogens.
authors.forename: Kavindra V
authors.initials: KV
authors.lastname: Singh
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, The Netherlands.
authors.forename: Xinglin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, The Netherlands.
authors.forename: Willem
authors.initials: W
authors.lastname: van Schaik
authors.affiliation: Center for Infectious Disease and Travel Medicine, University Medical Center Freiburg, Germany.
authors.forename: Dominique
authors.initials: D
authors.lastname: Wobser
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, The Netherlands.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Braat
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases Center for the Study of Emerging and Re-emerging Pathogens Department of Microbiology and Molecular Genetics, University of Texas Health Science Center at Houston.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Murray
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, The Netherlands.
authors.forename: Marc J M
authors.initials: MJ
authors.lastname: Bonten
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, The Netherlands.
authors.forename: Rob J L
authors.initials: RJ
authors.lastname: Willems
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, The Netherlands.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Leavis
mesh_terms: D000818:Animals; D018441:Biofilms / Q000254:growth & development*; D004251:DNA Transposable Elements; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000382:microbiology* / Q000503:physiopathology*; D016984:Enterococcus faecium / Q000201:enzymology* / Q000472:pathogenicity / Q000502:physiology*; D005260:Female; D055786:Gene Knockout Techniques; D005820:Genetic Testing; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D016254:Mutagenesis, Insertional; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements; D026901:Membrane Transport Proteins; D037521:Virulence Factors; D010770:Phosphotransferases
keywords: E. faecium; biofilm; endocarditis; phosphotransferase system