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

抑制牙周病原牙龈卟啉单胞菌从口腔环境中获取铁的新药的研究。

基本信息

批准号：
13557149
负责人：
NAKAYAMA Koji
金额：
$ 7.68万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

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.

口腔厌氧菌牙龈卟啉单胞菌被认为是牙周炎的重要病原体。检查了非铁金属卟啉、铟原卟啉 (In-PPIX) 对牙龈卟啉单胞菌的抗菌作用。 In-PPIX 以剂量依赖性方式显示出对牙龈卟啉单胞菌的生长抑制。 p的ihtB突变体。 gingivalis 比野生型亲本对 In-PPIX 具有更强的抗性，而 hmuR 突变体则更敏感，表明 In-PPIX 可能通过 IhtB 介导的铁吸收途径掺入。牙龈卟啉单胞菌的 sod 突变体对 In-PPIX 表现出几乎相同的敏感性，这与大肠杆菌 SOD 无效突变体对镓原卟啉表现出过敏的发现形成鲜明对比。此外，牙龈卟啉单胞菌dps突变体比野生型亲本表现出对In-PPIX更强的抵抗力，这表明作为含铁蛋白之一的Dps蛋白可能与In-PPIX毒性有关。我们已经发现乳铁蛋白及其活性肽结构域乳铁素具有抑制牙龈卟啉单胞菌生长的能力。乳铁蛋白从牙龈卟啉单胞菌细胞表面去除血红蛋白受体蛋白 (HbR)，从而抑制生长。这种抑制系统似乎与 In-PPIX 的不同，表明两种化学物质的使用可能对牙龈卟啉单胞菌的生长表现出协同作用。