Human lactoferrin binds and removes the hemoglobin receptor protein of the periodontopathogen Porphyromonas gingivalis.
Porphyromonas gingivalis possesses a hemoglobin receptor (HbR) protein on the cell surface as one of the major components of the hemoglobin utilization system in this periodontopathogenic bacterium. HbR is intragenically encoded by the genes of an arginine-specific cysteine proteinase (rgpA), lysine-specific cysteine proteinase (kgp), and a hemagglutinin (hagA). Here, we have demonstrated that human lactoferrin as well as hemoglobin have the abilities to bind purified HbR and the cell surface of P. gingivalis through HbR. The interaction of lactoferrin with HbR led to the release of HbR from the 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 for 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 cells as human lactoferrin, indicating that the effects of lactoferrin might be attributable to the lactoferricin region. These results suggest that lactoferrin has a bacteriostatic action on P. gingivalis by binding HbR, removing it from the cell surface, and consequently disrupting the iron uptake system from hemoglobin.
Shi
Y
Y
Department of Microbiology, Faculty of Dentistry, Kyushu University, Fukuoka 812-8582, Japan.
Kong
W
W
Nakayama
K
K
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003470:Culture Media / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007781:Lactoferrin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D008954:Models, Biological; D009154:Mutation; D010455:Peptides; D010518:Periodontitis / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003470:Culture Media; D006454:Hemoglobins; C094109:HmbR protein, Neisseria meningitidis; D010455:Peptides; D011956:Receptors, Cell Surface; C082171:lactoferricin B; D007781:Lactoferrin