Sensitivity of Periodontal Pathogens to the Bactericidal Activity of Synthetic Protegrins, Antibiotic Peptides Derived from Porcine Leukocytes

Protegrins, small peptides (1900 to 2160 daltons) isolated from porcine leukocytes, are bactericidal against a broad range of medical pathogens in vitro under conditions which reflect the extracellular milieu. The purpose of this study was to determine whether Gram-negative, facultative periodontal pathogens were sensitive to the protegrins. Synthetic L- and D-enantiomers of protegrin 1 (PG-1 and D-PG-1, respectively), and L-enantiomers of protegrins 2, 3, and 5 (PG-2, PG-3, and PG-5) were tested against Actinobacillus actinomycetemcomitans (three strains) and Capnocytophaga spp. (three strains). Strains of both A. actinomycetemcomitans and Capnocytophaga spp. were sensitive to PG-1, and exhibited ED99 (dose at which 99% killing was observed after 1 hr at 37°C) of 0.5 to 3 ug/mL and 4 to 19 ug/mL, respectively. The D-form and the L-form were equally effective. Serum (above 5% v/v) inhibited the bactericidal effects of 10 ug/mL PG-1, but the inhibitory effect was overcome by concentrations of PG-1 at 100 ug/mL. Different patterns of sensitivity were observed when the effects of PG-1, D-PG-1, PG-2, PG-3, and PG-5 were compared against A. actinomycetemcomitans and the Capnocytophaga. We conclude that protegrins may be useful antimicrobial agents in therapy against periodontal infections.