Targeting pili in enterococcal pathogenesis.
Passive protection, the administration of antibodies to prevent infection, has garnered significant interest in recent years as a potential prophylactic countermeasure to decrease the prevalence of hospital-acquired infections. Pili, polymerized protein structures covalently anchored to the peptidoglycan wall of many Gram-positive pathogens, are ideal targets for antibody intervention, given their importance in establishing infection and their accessibility to antibody interactions. In this work, we demonstrated that a monoclonal antibody to the major component of Enterococcus faecalis pili, EbpC, labels polymerized pilus structures, diminishes biofilm formation, and significantly prevents the establishment of a rat endocarditis infection. The effectiveness of this anti-EbpC monoclonal provides strong evidence in support of its potential as a preventative. In addition, after radiolabeling, this monoclonal identified the site of enterococcal infection, providing a rare example of molecularly specific imaging of an established bacterial infection and demonstrating the versatility of this agent for use in future diagnostic and therapeutic applications.
Center for Molecular Imaging, Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Kenneth L
KL
Pinkston
Kavindra V
KV
Singh
Peng
P
Gao
Nathaniel
N
Wilganowski
Holly
H
Robinson
Sukhen
S
Ghosh
Ali
A
Azhdarinia
Eva M
EM
Sevick-Muraca
Barbara E
BE
Murray
Barrett R
BR
Harvey
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D018441:Biofilms / Q000254:growth & development; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D013293:Enterococcus faecalis / Q000276:immunology*; D036781:Fimbriae Proteins / Q000276:immunology; D010861:Fimbriae, Bacterial / Q000276:immunology*; D016908:Gram-Positive Bacterial Infections / Q000276:immunology / Q000517:prevention & control*; D007116:Immunization, Passive / Q000379:methods*; D051381:Rats
D000911:Antibodies, Monoclonal; D036781:Fimbriae Proteins