Investigation of New Drugs that Inhibit Acquisition of Iron from Oral Environments in the Periodontopathogen Porphyromonas gingivalis.

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The oral anaerobic bacterium Porphyromonas gingivalis is implicated as an important pathogen for periodontitis. A non-iron metalloporphyrin, indium-protoporphyrin (In-PPIX) was examined for antibacterial effects on P. gingivalis. In-PPIX showed growth inhibition of P. gingivalis in a dose-dependent fashion. An ihtB mutant of p. gingivalis was more resistant to In-PPIX than the wild type parent, while an hmuR mutant was more sensitive, indicating that In-PPIX might be incorporated by the IhtB-mediated iron uptake pathway. An sod mutant of P. gingivalis showed almost the same sensitivity to In-PPIX, which was contrast with the finding that E. coil SOD-null mutant shows hypersensitive to galium-protoporphyrin. Moreover, P. gingivalis dps mutant showed more resistant to In-PPIX than the wild type parent, suggesting that Dps protein which is one of iron-containing proteins might be related with In-PPIX toxicity. We already found that lactoferrin and its active peptide domain, lactoferricin have the ability to inhibit growth of P. gingivalis. Lactoferrin removes the hemoglobin receptor protein (HbR) from the P. gingivalis cell surface with the result of growth inhibition. This inhibition system seems to be different from that of In-PPIX, suggesting that use of both chemicals may show a synergistic effect on growth of P. gingivalis.