In Vitro and In Vivo Anti-infective Potential of Thymol Against Early Childhood Caries Causing Dual Species Candida albicans and Streptococcus mutans

Priya, Arumugam; Selvaraj, Anthonymuthu; Divya, D.; Raja, Ramalingam Karthik; Pandian, Shunmugiah Karutha

doi:10.3389/fphar.2021.760768

Cited by 18 publications

(18 citation statements)

References 69 publications

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“…Moreover, thymol showed a dose-dependent reduction in acidogenesis of Str. mutans and reduced the expression of multiple virulence-associated genes, including the gtfB gene also investigated in this study (Priya et al, 2021). Because these results are reminiscent of the data presented here, this supports our hypothesis that thymol is one of the main active components of the O. vulgare ethanolic extract.…”

Section: Discussionsupporting

confidence: 91%

“…The only virulence-associated gene under study that was not significantly affected by extract treatment was an enterococcal gelatinase (gelE), which has been implicated in the degradation of dentin (Lee and Tan, 2015). Although some studies have reported that other bioactive compounds can influence Gtf activity, acidogenesis and expression of the selected virulenceassociated genes in cariogenic bacteria, this is the first report that describes those effects for an O. vulgare extract (Furiga et al, 2008;Lee and Tan, 2015;Khan et al, 2016;Shafiei et al, 2020;Priya et al, 2021;Reis et al, 2021). Especially against the backdrop of an antimicrobial resistance crisis, anti-virulence properties are believed to be more robust to the development of resistance and provide an attractive complementation to the more conventionally studied bacteriostatic and bactericidal activities (Dickey et al, 2017).…”

Section: Discussionmentioning

confidence: 96%

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Origanum vulgare ethanolic extracts as a promising source of compounds with antimicrobial, anti-biofilm, and anti-virulence activity against dental plaque bacteria

Idir

Ginneken²,

Coppola³

et al. 2022

Front. Microbiol.

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Dental caries and periodontal diseases remain a challenge for oral health, especially given the lack of effective and safe treatment options that are currently available. Against the backdrop of an ongoing antimicrobial resistance crisis, a renewed interest in traditional medicinal plants as a potential source of new bioactive compounds has surfaced. In this context, we systematically screened the antimicrobial and anti-biofilm activities of both ethanolic and aqueous extracts of nine Algerian medicinal plants (Artemisia herba alba, Centaurium erythraea, Juglans regia, Laurus nobilis, Matricaria recutita, Mentha pulegium, Mentha piperita, Origanum vulgare and Taraxacum officinale). To evaluate the activity spectrum of the extracts, the screening was carried out against an extensive collection of Streptococcus, Enterococcus and Lacticaseibacillus isolates recovered from dental plaques of Algerian patients. Broad-spectrum antimicrobial and anti-biofilm properties were observed, especially among ethanolic extracts, which marks them as a promising source for bioactive compounds to control oral biofilms. The ethanolic extract of O. vulgare, which showed the most promising effects in the initial screening, was further characterized. We first verified the biocompatibility of this extract using human oral keratinocytes and selected a range of non-cytotoxic concentrations (0.195–0.781 mg/ml) to further validate its anti-biofilm and anti-virulence potential. At these concentrations, the extract not only prevented biofilm formation (10.04 ± 0.75–87.91 ± 9.08% of reduction) of most dental plaque isolates on a polystyrene surface, but also significantly reduced their adherence to hydroxyapatite (34.58 ± 9.09–62.77 ± 0.95%). Moreover, the extract showed curative potential against mature biofilms grown under conditions mimicking the oral niche. In addition to its anti-biofilm properties, we observed an inhibition of glucosyltransferase activity, a reduction in acidogenesis and a downregulation in the expression of multiple virulence-associated genes for extract-treated samples. Since anti-virulence properties are more robust to the development of resistance, they provide an attractive complementation to the antimicrobial activities of the extract. Thymol was identified as an important active compound of the extract using GC–MS analysis, but synergy with other compounds was also detected, suggesting a potential advantage of using the whole extract over purified thymol. Further research into the bioactive compounds of the O. vulgare ethanolic extract could yield novel products to fight dental caries.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 96%

Origanum vulgare ethanolic extracts as a promising source of compounds with antimicrobial, anti-biofilm, and anti-virulence activity against dental plaque bacteria

Idir

Ginneken²,

Coppola³

et al. 2022

Front. Microbiol.

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“…Thymol significantly reduced the biofilm formation and virulence of both S. mutans and C. albicans, including acidogenicity (acid production from the dietary carbohydrates), acidurity (able to survive under lethal pH condition), and yeast-to-hyphal transition, in single- and mixed-species biofilm communities. Notably, these microorganisms did not show resistance against thymol, which could be associated with the fact that this compound showed regulatory effects on many genes/transcriptional regulators of both organisms ( Priya et al, 2021b ). The synergistic interaction between S. mutans and C. albicans within the carious biofilm leads to enhanced virulence of both pathogens.…”

Section: Thymolmentioning

confidence: 99%

“…The synergistic interaction between S. mutans and C. albicans within the carious biofilm leads to enhanced virulence of both pathogens. Recent investigations have demonstrated that the presence of C. albicans supports the extensive colonization of S. mutans in the dental biofilm ( Waltimo et al, 2000 ; Priya et al, 2021b ). Thus, thymol, due to its ability to inhibit fungal filamentation and morphogenesis, and impair S. mutans acidogenic and aciduric ability, could be a practical candidate for the prevention and treatment of early childhood caries; however, more confirmatory investigations are required.…”

Section: Thymolmentioning

confidence: 99%

Natural Compounds: A Hopeful Promise as an Antibiofilm Agent Against Candida Species

et al. 2022

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The biofilm communities of Candida are resistant to various antifungal treatments. The ability of Candida to form biofilms on abiotic and biotic surfaces is considered one of the most important virulence factors of these fungi. Extracellular DNA and exopolysaccharides can lower the antifungal penetration to the deeper layers of the biofilms, which is a serious concern supported by the emergence of azole-resistant isolates and Candida strains with decreased antifungal susceptibility. Since the biofilms’ resistance to common antifungal drugs has become more widespread in recent years, more investigations should be performed to develop novel, inexpensive, non-toxic, and effective treatment approaches for controlling biofilm-associated infections. Scientists have used various natural compounds for inhibiting and degrading Candida biofilms. Curcumin, cinnamaldehyde, eugenol, carvacrol, thymol, terpinen-4-ol, linalool, geraniol, cineole, saponin, camphor, borneol, camphene, carnosol, citronellol, coumarin, epigallocatechin gallate, eucalyptol, limonene, menthol, piperine, saponin, α-terpineol, β–pinene, and citral are the major natural compounds that have been used widely for the inhibition and destruction of Candida biofilms. These compounds suppress not only fungal adhesion and biofilm formation but also destroy mature biofilm communities of Candida. Additionally, these natural compounds interact with various cellular processes of Candida, such as ABC-transported mediated drug transport, cell cycle progression, mitochondrial activity, and ergosterol, chitin, and glucan biosynthesis. The use of various drug delivery platforms can enhance the antibiofilm efficacy of natural compounds. Therefore, these drug delivery platforms should be considered as potential candidates for coating catheters and other medical material surfaces. A future goal will be to develop natural compounds as antibiofilm agents that can be used to treat infections by multi-drug-resistant Candida biofilms. Since exact interactions of natural compounds and biofilm structures have not been elucidated, further in vitro toxicology and animal experiments are required. In this article, we have discussed various aspects of natural compound usage for inhibition and destruction of Candida biofilms, along with the methods and procedures that have been used for improving the efficacy of these compounds.

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“…Polyphenol extracts from green tea or cranberries have also been shown to effectively inhibit the acidogenicity and metabolic activity of C. albicans-S. mutans biofilms, decrease EPS and microbial biovolumes, and disrupt biofilm structure (59,60). Thymol, the major constituent of thyme essential oil, is another nature product that showed ability to diminish the C. albicans-S. mutans dual-species biofilm formation and virulence (61). In addition, thymol was found to be effective in diminishing C. albicans-S. mutans dual-species virulence in the invertebrate model Galleria mellonella (61).…”

Section: Approaches To Disrupt C Albicans-s Mutans Biofilmmentioning

confidence: 99%

Candida albicans and Early Childhood Caries

et al. 2022

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Early childhood caries (ECC) is a highly prevalent and costly chronic oral infectious disease in preschool children. Candida albicans has been frequently detected in children and has demonstrated cariogenic traits. However, since ECC is a multifactorial infectious disease with many predisposing non-microbial factors, it remains to be elucidated whether the presence and accumulation of C. albicans in ECC is merely a consequence of the adaptation of C. albicans to a cariogenic oral environment, or it plays an active role in the initiation and progression of dental caries. This review aims to summarize the current knowledge on C. albicans and the risk of ECC, with a focus on its synergistic relationship with the cariogenic pathogen Streptococcus mutans. We also highlight recent advances in the development of approaches to disrupt C. albicans-S. mutans cross-kingdom biofilms in ECC prevention and treatment. Longitudinal clinical studies, including interventional clinical trials targeting C. albicans, are necessary to ascertain if C. albicans indeed contributes in a significant manner to the initiation and progression of ECC. In addition, further work is needed to understand the influence of other bacteria and fungi of oral microbiota on C. albicans-S. mutans interactions in ECC.

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In Vitro and In Vivo Anti-infective Potential of Thymol Against Early Childhood Caries Causing Dual Species Candida albicans and Streptococcus mutans

Cited by 18 publications

References 69 publications

Origanum vulgare ethanolic extracts as a promising source of compounds with antimicrobial, anti-biofilm, and anti-virulence activity against dental plaque bacteria

Origanum vulgare ethanolic extracts as a promising source of compounds with antimicrobial, anti-biofilm, and anti-virulence activity against dental plaque bacteria

Natural Compounds: A Hopeful Promise as an Antibiofilm Agent Against Candida Species

Candida albicans and Early Childhood Caries

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