Targeted antimicrobial activity of a specific IgG-SMAP28 conjugate against Porphyromonas gingivalis in a mixed culture

Int J Antimicrob Agents. 2009 Jan;33(1):14-20. doi: 10.1016/j.ijantimicag.2008.05.021. Epub 2008 Sep 7.

Abstract

Antimicrobial peptides coupled to a ligand, receptor or antibody for a specific pathogenic bacteria could be used to develop narrow-spectrum pharmaceuticals with 'targeted' antimicrobial activity void of adverse reactions often associated with the use of broad-spectrum antibiotics. To assess the feasibility of this approach, in this study sheep myeloid antimicrobial peptide (SMAP) 28 was linked to affinity- and protein G-purified rabbit immunoglobulin G (IgG) antibodies specific to the outer surface of Porphyromonas gingivalis strain 381. The selective activity of the P. gingivalis IgG-SMAP28 conjugate was then assessed by adding it to an artificially generated microbial community containing P. gingivalis, Aggregatibacter actinomycetemcomitans and Peptostreptococcus micros. The specificity of the P. gingivalis IgG-SMAP28 conjugate in this mixed culture was concentration-dependent. The conjugate at 50 microg protein/mL lacked specificity and killed P. gingivalis, A. actinomycetemcomitans and P. micros. The conjugate at 20 microg protein/mL was more specific and killed P. gingivalis. This is an initial step to develop a selective antimicrobial agent that can eliminate a specific periodontal pathogen, such as P. gingivalis, from patients with periodontal disease without harming the normal commensal flora.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Bacterial / chemistry
  • Antibodies, Bacterial / immunology
  • Antibodies, Bacterial / pharmacology*
  • Antibody Specificity*
  • Antimicrobial Cationic Peptides / chemical synthesis
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology*
  • Cross-Linking Reagents / chemistry
  • Culture Media
  • Ecosystem
  • Humans
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / pharmacology*
  • Maleimides / chemistry
  • Microbial Sensitivity Tests / methods
  • Pasteurellaceae / growth & development
  • Peptostreptococcus / growth & development
  • Porphyromonas gingivalis / drug effects*
  • Porphyromonas gingivalis / growth & development
  • Porphyromonas gingivalis / immunology
  • Sheep

Substances

  • Antibodies, Bacterial
  • Antimicrobial Cationic Peptides
  • Cross-Linking Reagents
  • Culture Media
  • Immunoglobulin G
  • Maleimides
  • maleimide