An early report: a modified porphyrin-linked metronidazole targeting intracellular Porphyromonas gingivalis in cultured oral epithelial cells

作     者：Ping Ye Jiho Chang Lin Feng Foo Benjamin C-M Yap Ping Ye Jiho Chang Lin Feng Foo Benjamin C-M Yap

作者机构：Institute of Dental Research Centre for Oral Health Westmead Hospital Affiliation of Faculty of Dentistry the University of Sydney 

出 版 物：《International Journal of Oral Science》 (国际口腔科学杂志（英文版）)

年 卷 期：2017年第9卷第3期

页      面：167-173页

核心收录：

学科分类：1003[医学-口腔医学] 100302[医学-口腔临床医学] 10[医学] 

基　　金：supported by the Postgraduate Research Program from The University of Sydney 

主　　题：porphyrin-linked metronidazole Porphyromonas gingivalis periodontitis oral epithelial cells 

摘      要：Porphyromonas gingivalis （P. gingivalis） has a strong association with the pathogenesis of periodontal disease. Recurrence of periodontal disease following therapy is attributed to numerous factors, and of growing interest is the potential problem of intracellular bacteria that are able to persist and multiply within the host cell, thereby facilitating relapse of infection. The effect of antibiotic therapy in controlling P. gingivalis is questionable. Accordingly, while metronidazole is very effective against anaerobic extracellular P. gingivalis by disrupting the DNA of anaerobic microbial cells, this antibiotic does not effectively penetrate into mammalian cells to inhibit intracellular bacteria. Therefore in the present study, a modified porphyrin-linked metronidazole adducts, developed in our laboratory, was used to kill intracellular P. gingivalis. A series of experiments were performed, including cytotoxicity assays and cellular uptake of adducts by flow cytometry coupled with live cell imaging analysis, P. gingivalis invasion and elimination assays, and the analysis of colocalization of P. gingivalis and porphyrin-linked metronidazole by confocal laser scanning microscopy. Findings indicated that P. gingivalis and porphyrin-linked metronidazole were colocalized in the cytoplasm, and this compound was able to kill P. gingivalis intracellular with a sufficient culture time. This is a novel antimicrobial approach in the elimination of P. gingivalis from the oral cavity.