Repurposing Napabucasin as an Antimicrobial Agent against Oral Streptococcal Biofilms

Abstract

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.

A Novel Small Molecule, LCG-N25, Inhibits Oral Streptococcal Biofilm

“…Our data showed that LCG-N25 exhibited significantly lower cytotoxicity on HOKs and HGEs as compared to CHX and NAP. In addition, the antimicrobial activities of LCG-N25 against oral streptococci were significantly enhanced after structural modifications, with almost an eight-fold decrease of MIC against S. mutans as compared to that of NAP (3.91 µg/mL as reported previously) (Kuang et al, 2020), and a 3-fold decrease in MIC as compared to that of CHX. All these data indicate that LCG-N25 is more suitable for the control of oral biofilms as compared to its lead compound NAP.…”

“…* Statistically significant differences compared to the control (P < 0.05); ns, not significant. previously screened a library of bioactive molecules against S. mutans and identified a natural compound NAP showing good antimicrobial activity against oral streptococci (Kuang et al, 2020). However, as an antitumor treatment currently in phase III clinical trials (Sonbol et al, 2019), the mild cytotoxicity of NAP on oral cells may limit its repurposed used in the control of dental caries.…”

“…Previous studies have demonstrated that structural modification of lead compounds can enhance its inhibitory activity against microorganisms, as well as improve its cell potency and pharmacokinetic profiles but reduce its toxicity to human cells ( Yang et al, 2019 ; Shi et al, 2020 ; Zhang et al, 2020 ). We previously screened a library of bioactive molecules against S. mutans and identified a natural compound NAP showing good antimicrobial activity against oral streptococci ( Kuang et al, 2020 ). However, as an antitumor treatment currently in phase III clinical trials ( Sonbol et al, 2019 ), the mild cytotoxicity of NAP on oral cells may limit its repurposed used in the control of dental caries.…”

“…Small molecules have shown inhibitory effect on bacterial biofilms due to its good antimicrobial activity, good stability, and low toxicity ( Worthington et al, 2012 ). In our previous study, we screened from a library of bioactive molecules against S. mutans and identified a natural compound napabucasin (NAP) (2-acetylfuro-1,4-naphathoquinone) isolated from Newbouldia laevis , showing antimicrobial activity against oral streptococci ( Kuang et al, 2020 ). However, NAP as an antitumor treatment currently in phase III clinical trials shows mild cytotoxic effects on oral cells, and its antimicrobial activities against oral streptococci are relatively lower than CHX.…”

Corrigendum to “Repurposing Napabucasin as an Antimicrobial Agent against Oral Streptococcal Biofilms”

“…In the article titled “Repurposing Napabucasin as an Antimicrobial Agent against Oral Streptococcal Biofilms” [ 1 ], the authors mistakenly generated the line graph of Figure 1(c) using the data from Figure 1(b) . The corrected figure is provided as follows.…”