Human lactoferrin binds and removes the hemoglobin receptor protein of theperiodontopathogen Porphyromonas gingivalis

Porphyromonas gingivalis possesses a hemoglobin receptor (HbR) protein on t he cell surface as one of the major components of the hemoglobin utilizatio n system in this periodontopathogenic bacterium. HbR is intragenically enco ded by the genes of an arginine-specific cysteine proteinase (rgpA), lysine -specific cysteine proteinase (kgp), and a hemagglutinin (hagA). Here, we h ave demonstrated that human lactoferrin as well as hemoglobin have the abil ities to bind purified HbR and the cell surface of P. gingivalis through Hb R. The interaction of lactoferrin with HbR led to the release of HbR from t he cell surface of P. gingivalis. This lactoferrin-mediated HbR release was inhibited by the cysteine proteinase inhibitors effective to the cysteine proteinases of P. gingivalis. P. gingivalis could not utilize lactoferrin f or its growth as an iron source and, in contrast, lactoferrin inhibited the growth of the bacterium in a rich medium containing hemoglobin as the sole iron source. Lactoferricin B, a 25-amino acid-long peptide located at the N-lobe of bovine lactoferrin, caused the same effects on P. gingivalis cell s as human lactoferrin, indicating that the effects of lactoferrin might be attributable to the lactoferricin region. These results suggest that lacto ferrin has a bacteriostatic action on P. gingivalis by binding HbR, removin g it from the cell surface, and consequently disrupting the iron uptake sys tem from hemoglobin.