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

Abstract

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.

Evaluating the effectiveness of clarithromycin as an adjunct to scaling and root planing: A randomized clinical trial

“…Although CLM has not been widely used in periodontal therapy, it was shown to be effective against “Aa” and several other periodontal pathogens, as it can reach bacteria that have invaded oral epithelium. [31] In combination with results from previous studies,[323334] the current findings suggest that CLM could be useful for treating periodontitis. However, an affirmative effect of CLM is very narrow.…”

Personalized and Defect-Specific Antibiotic-Laden Scaffolds for Periodontal Infection Ablation

“…MET promotes free-radical formation that interacts with bacteria DNA, resulting in loss of the helical DNA structure and strand breakage. 55 On the other hand, tetracycline, a broad-spectrum antimicrobial, inhibits bacterial protein synthesis. As an additional advantage, tetracyclines can inhibit collagenase, 56 contributing to minimizing tissue breakdown.…”

Carbon dot composites for bioapplications: a review

“…Metronidazole (MET), as an antibiotic, can cause strand damage to the bacterial DNA through the reduction of its nitro-group by an electron transport protein. 299 Madadi et al reported that conjugated cCQD-MET could rapidly internalize into H413 cells and exhibit enhanced antimicrobial activity. 300 In a different study, the CDs@PtPor composite demonstrated strong photocytotoxicity under light irradiation and therapeutic efficacy as well as low side effects in vitro , which was developed as a drug nanocarrier in cancer therapy.…”

“…For instance, in Yan and co-workers’ study, glyoxylic acid-modified CDs (GA-CDs) were used as a FRET ratiometric fluorescent probe for the detection of Cu 2+ in aqueous solution. 388 Similarly, Chen et al also applied cyclam-functionalized CDs as a FRET nanoprobe for the detection of Cu 2+ and S. 2–389 In addition to the above examples, the detection of other important metal ions such as Ag + , Cu 2+ , Cr 6+ , and Pb 2+ has also been successfully realized with CD composite-based sensing platforms. 390–401…”