Repurposing Toremifene for Treatment of Oral Bacterial Infections.
The spread of antibiotic resistance and the challenges associated with antiseptics such as chlorhexidine have necessitated a search for new antibacterial agents against oral bacterial pathogens. As a result of failing traditional approaches, drug repurposing has emerged as a novel paradigm to find new antibacterial agents. In this study, we examined the effects of the FDA-approved anticancer agent toremifene against the oral bacteria Porphyromonas gingivalis and Streptococcus mutans We found that the drug was able to inhibit the growth of both pathogens, as well as prevent biofilm formation, at concentrations ranging from 12.5 to 25 μM. Moreover, toremifene was shown to eradicate preformed biofilms at concentrations ranging from 25 to 50 μM. In addition, we found that toremifene prevents P. gingivalis and S. mutans biofilm formation on titanium surfaces. A time-kill study indicated that toremifene is bactericidal against S. mutans Macromolecular synthesis assays revealed that treatment with toremifene does not cause preferential inhibition of DNA, RNA, or protein synthesis pathways, indicating membrane-damaging activity. Biophysical studies using fluorescent probes and fluorescence microscopy further confirmed the membrane-damaging mode of action. Taken together, our results suggest that the anticancer agent toremifene is a suitable candidate for further investigation for the development of new treatment strategies for oral bacterial infections.
['Gerits|Evelien|E|', 'Defraine|Valerie|V|', 'Vandamme|Katleen|K|', 'De Cremer|Kaat|K|', 'De Brucker|Katrijn|K|', 'Thevissen|Karin|K|', 'Cammue|Bruno P A|BP|', 'Beullens|Serge|S|', 'Fauvart|Maarten|M|', 'Verstraeten|Natalie|N|', 'Michiels|Jan|J|']
D000900:Anti-Bacterial Agents D018931:Antineoplastic Agents, Hormonal D018441:Biofilms D002462:Cell Membrane D002463:Cell Membrane Permeability D003773:Dental Plaque D058492:Drug Repositioning D024901:Drug Resistance, Multiple, Bacterial D006801:Humans D008826:Microbial Sensitivity Tests D010518:Periodontitis D016966:Porphyromonas gingivalis D013295:Streptococcus mutans D014025:Titanium D017312:Toremifene
toremifene Porphyromonas gingivalis Streptococcus mutans biofilms oral infections