title: Enterococcal virulence determinants may be involved in resistance to clinical therapy.
abstract: The ability of enterococci to acquire resistance to antibiotics and form biofilms in vivo makes these infections, endocarditis in particular, especially difficult to treat. A collection of clinical enterococcal isolates was screened for the presence of various virulence determinants and in an in vitro assay for biofilm formation. Isolates were chosen for the presence or absence of the genes for Esp and gelatinase and different in vitro biofilm phenotypes, and were evaluated in a rat model of endocarditis; all colonized vegetations to similar degrees. Treatment with vancomycin resulted in a 2.7-log reduction in colony-forming unit (CFU) in vegetations for an esp(+)/gel(-) strain, compared with no reduction in CFU for an esp(+)/gel(+) or an esp(-)/gel(-) isolate. These results suggest that although there may not be an absolute role for individual virulence determinants in infectivity, combinations of factors may play a role in allowing a biofilm infection to be more resistant to therapy.
authors.affiliation: Pfizer Global Research and Development, Groton, CT 06340, USA. andrea.marra@pfizer.com
authors.forename: Andrea
authors.initials: A
authors.lastname: Marra
authors.forename: Fadia
authors.initials: F
authors.lastname: Dib-Hajj
authors.forename: Lucinda
authors.initials: L
authors.lastname: Lamb
authors.forename: Frank
authors.initials: F
authors.lastname: Kaczmarek
authors.forename: Wenchi
authors.initials: W
authors.lastname: Shang
authors.forename: Gretchen
authors.initials: G
authors.lastname: Beckius
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Milici
authors.forename: Ivette
authors.initials: I
authors.lastname: Medina
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Gootz
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D015169:Colony Count, Microbial; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D013293:Enterococcus faecalis / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D018093:Gelatinases / Q000235:genetics; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use; D020713:Vancomycin Resistance / Q000235:genetics; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; C116707:enterococcal surface protein, esp; D014640:Vancomycin; D018093:Gelatinases