title: SgrA, a nidogen-binding LPXTG surface adhesin implicated in biofilm formation, and EcbA, a collagen binding MSCRAMM, are two novel adhesins of hospital-acquired Enterococcus faecium.
abstract: Hospital-acquired Enterococcus faecium isolates responsible for nosocomial outbreaks and invasive infections are enriched in the orf2351 and orf2430 genes, encoding the SgrA and EcbA LPXTG-like cell wall-anchored proteins, respectively. These two surface proteins were characterized to gain insight into their function, since they may have favored the rapid emergence of this nosocomial pathogen. We are the first to identify a surface adhesin among bacteria (SgrA) that binds to the extracellular matrix molecules nidogen 1 and nidogen 2, which are constituents of the basal lamina. EcbA is a novel E. faecium MSCRAMM (microbial surface component recognizing adhesive matrix molecules) that binds to collagen type V. In addition, both SgrA and EcbA bound to fibrinogen; however, SgrA targeted the alpha and beta chains, whereas EcbA bound to the gamma chain of fibrinogen. An E. faecium sgrA insertion mutant displayed reduced binding to both nidogens and fibrinogen. SgrA did not mediate binding of E. faecium cells to biotic materials, such as human intestinal epithelial cells, human bladder cells, and kidney cells, while this LPXTG surface adhesin is implicated in E. faecium biofilm formation. The acm and scm genes, encoding two other E. faecium MSCRAMMs, were expressed at the mRNA level together with sgrA during all phases of growth, whereas ecbA was expressed only in exponential and late exponential phase, suggesting orchestrated expression of these adhesins. Expression of these surface proteins, which bind to extracellular matrix proteins and are involved in biofilm formation (SgrA), may contribute to the pathogenesis of hospital-acquired E. faecium infections.
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, Rm. G04.614, 3584 CX Utrecht, The Netherlands. a.hendrickx@umcutrecht.nl
authors.forename: Antoni P A
authors.initials: AP
authors.lastname: Hendrickx
authors.forename: Miranda
authors.initials: M
authors.lastname: van Luit-Asbroek
authors.forename: Claudia M E
authors.initials: CM
authors.lastname: Schapendonk
authors.forename: Willem J B
authors.initials: WJ
authors.lastname: van Wamel
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Braat
authors.forename: Lucas M
authors.initials: LM
authors.lastname: Wijnands
authors.forename: Marc J M
authors.initials: MJ
authors.lastname: Bonten
authors.forename: Rob J L
authors.initials: RJ
authors.lastname: Willems
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D001422:Bacterial Adhesion / Q000235:genetics; D018441:Biofilms; D015139:Blotting, Southern; D015153:Blotting, Western; D003094:Collagen / Q000378:metabolism; D003428:Cross Infection / Q000235:genetics* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D016984:Enterococcus faecium / Q000472:pathogenicity / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial; D016908:Gram-Positive Bacterial Infections / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018829:Adhesins, Bacterial; D008562:Membrane Glycoproteins; C029967:nidogen; D003094:Collagen