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Repurposing Napabucasin as an Antimicrobial Agent against Oral Streptococcal Biofilms
BioMed Research International ( IF 2.6 ) Pub Date : 2020-11-21 , DOI: 10.1155/2020/8379526
Xinyi Kuang 1 , Tao Yang 2 , Chenzi Zhang 1 , Xian Peng 1 , Yuan Ju 3 , Chungen Li 2, 3 , Xuedong Zhou 1 , Youfu Luo 3 , Xin Xu 1
Affiliation  

Objectives. Disruption of microbial biofilms is an effective way to control dental caries. Drug resistance and side effects of the existing antimicrobials necessitate the development of novel antibacterial agents. The current study was aimed at investigating the antibacterial activities of the repurposed natural compound napabucasin against oral streptococci. Methods. The minimum inhibitory concentration, minimum bactericidal concentration, minimum biofilm inhibition concentration, and minimum biofilm reduction concentration of Streptococcus mutans, Streptococcus gordonii, and Streptococcus sanguinis were examined by a microdilution method. Cytotoxicity of napabucasin against human oral keratinocytes, human gingival epithelia, and macrophage RAW264.7 was evaluated by CCK8 assays. The dead/live bacterium and exopolysaccharide in the napabucasin-treated multispecies biofilms were evaluated by confocal laser scanning microscopy. Microbial composition within the napabucasin-treated biofilms was further visualized by fluorescent in situ hybridization and qPCR. And the cariogenicity of napabucasin-treated biofilms was evaluated by transverse microradiography. Results. Napabucasin exhibited good antimicrobial activity against oral streptococcal planktonic cultures and biofilms but with lessened cytotoxicity as compared to chlorhexidine. Napabucasin reduced the cariogenic S. mutans and increased the proportion of the commensal S. gordonii in the multispecies biofilms. More importantly, napabucasin significantly reduced the demineralization capability of biofilms on tooth enamels. Conclusion. Napabucasin shows lessened cytotoxicity and comparable antimicrobial effects to chlorhexidine. Repurposing napabucasin may represent a promising adjuvant for the management of dental caries.

中文翻译:

重新利用 Napabucasin 作为抗口腔链球菌生物膜的抗菌剂

目标。破坏微生物生物膜是控制龋齿的有效方法。现有抗菌剂的耐药性和副作用需要开发新型抗菌剂。目前的研究旨在调查重新利用的天然复合物萘帕布卡辛对口腔链球菌的抗菌活性。方法变形链球菌、戈登链球菌血链球菌最低抑菌浓度、最低杀菌浓度、最低生物膜抑制浓度、最低生物膜还原浓度采用微量稀释法检测。通过 CCK8 测定评估萘布卡辛对人口腔角质形成细胞、人牙龈上皮细胞和巨噬细胞 RAW264.7 的细胞毒性。通过共聚焦激光扫描显微镜评估了napabucasin 处理的多物种生物膜中的死/活细菌和胞外多糖。通过荧光原位杂交和 qPCR 进一步观察了经过萘帕布卡辛处理的生物膜内的微生物组成。并且通过横向显微摄影评估了萘巴布卡辛处理的生物膜的致龋性。结果。Napabucasin 对口腔浮游链球菌培养物和生物膜表现出良好的抗菌活性,但与洗必泰相比,细胞毒性降低。Napabucasin 减少致龋性变形链球菌并增加了共生S. gordonii在多物种生物膜中的比例。更重要的是,napabucasin 显着降低了牙釉质上生物膜的脱矿能力。结论。Napabucasin 显示出降低的细胞毒性和与洗必泰相当的抗菌作用。再利用napabucasin 可能是治疗龋齿的有希望的佐剂。
更新日期:2020-11-22
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