The fibronectin-binding protein EfbA contributes to pathogenesis and protects against infective endocarditis caused by Enterococcus faecalis.
EfbA is a PavA-like fibronectin adhesin of Enterococcus faecalis previously shown to be important in experimental urinary tract infection. Here, we expressed and purified the E. faecalis OG1RF EfbA and confirmed that this protein binds with high affinity to immobilized fibronectin, collagen I, and collagen V. We constructed an efbA deletion mutant and demonstrated that its virulence was significantly attenuated (P < 0.0006) versus the wild type in a mixed inoculum rat endocarditis model. Furthermore, efbA deletion resulted in diminished ability to bind fibronectin (P < 0.0001) and reduced biofilm (P < 0.001). Reintroduction of efbA into the original chromosomal location restored virulence, adherence to fibronectin, and biofilm formation to wild-type levels. Finally, vaccination of rats with purified recombinant EfbA protein protected against OG1RF endocarditis (P = 0.008 versus control). Taken together, our results demonstrate that EfbA is an important factor involved in E. faecalis endocarditis and that rEfbA immunization is effective in preventing such infection, likely by interfering with bacterial adherence.
Department of Internal Medicine, Division of Infectious Diseases, University of Texas Health Science Center at Houston, Houston, Texas, USA Center for the Study of Emerging and Re-emerging Pathogens, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Kavindra V
KV
Singh
Department of Internal Medicine, Division of Infectious Diseases, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Sabina Leanti
SL
La Rosa
Department of Internal Medicine, Division of Infectious Diseases, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Sudha R
SR
Somarajan
Department of Internal Medicine, Division of Infectious Diseases, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Jung Hyeob
JH
Roh
Department of Internal Medicine, Division of Infectious Diseases, University of Texas Health Science Center at Houston, Houston, Texas, USA Center for the Study of Emerging and Re-emerging Pathogens, University of Texas Health Science Center at Houston, Houston, Texas, USA Department of Microbiology and Molecular Genetics, University of Texas Health Science Center at Houston, Houston, Texas, USA bem.asst@uth.tmc.edu.
Barbara E
BE
Murray
D018829:Adhesins, Bacterial / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001665:Binding Sites; D018441:Biofilms / Q000254:growth & development*; D024042:Collagen Type I / Q000276:immunology / Q000378:metabolism; D024062:Collagen Type V / Q000276:immunology / Q000378:metabolism; D004697:Endocarditis, Bacterial / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D013293:Enterococcus faecalis / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D005816:Genetic Complementation Test; D016908:Gram-Positive Bacterial Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D007114:Immunization; D009154:Mutation; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D018829:Adhesins, Bacterial; D024042:Collagen Type I; D024062:Collagen Type V; D005353:Fibronectins; D011994:Recombinant Proteins