In Vitro Impact of Fluconazole on Oral Microbial Communities, Bacterial Growth, and Biofilm Formation.

Antifungal agents are widely used to specifically eliminate infections by fungal pathogens. However, the specificity of antifungal agents has been challenged by a few studies demonstrating antibacterial inhibitory effects against Mycobacteria and Streptomyces species. Here, we evaluated for the first time the potential effect of fluconazole, the most clinically used antifungal agent, on a human oral microbiota biofilm model. The results showed that biofilm viability on blood and mitis salivarius agar media was increased over time in the presence of fluconazole at clinically relevant concentrations, despite a reduction in biomass. Targeted PCR revealed a higher abundance of Veillonella atypica, Veillonella dispar, and Lactobacillus spp. in the fluconazole-treated samples compared to the control, while Fusobacterium nucleatum was reduced and Streptococcus spp were not significantly affected. Further, we tested the potential impact of fluconazole using single-species models. Our results, using Streptococcus mutans and Streptococcus mitis luciferase reporters, showed that S. mutans planktonic growth was not significantly affected by fluconazole, whereas for S. mitis, planktonic growth, but not biofilm viability, was inhibited at the highest concentration. Fluconazole's effects on S. mitis biofilm biomass were concentration and time dependent. Exposure for 48 h to the highest concentration of fluconazole was associated with S. mitis biofilms with the most increased biomass. Potential growth inhibitory effects were further tested using four non-streptococcal species. Among these, the planktonic growth of both Escherichia coli and Granulicatella adiacens was inhibited by fluconazole. The data indicate bacterial responses to fluconazole that extend to a broader range of bacterial species than previously anticipated from the literature, with the potential to disturb biofilm communities.

Can polyphenolic surface modifications prevent fungal colonization of titanium dental implants?

Oral biofilms can be a major health problem causing infections and chronic inflammation of mucosal tissue. While much effort is put in the investigation of bacteria in biofilms, the role of fungi is often neglected, despite Candida albicans playing a key role in the formation of multispecies oral biofilms. With the rise of antibiotic resistance, new strategies to reduce microbial growth need to be found. Therefore, plant derived polyphenolic molecules have been suggested to reduce both adhesion and growth of pathogenic bacteria and fungi. In this study, we investigated the use of polyphenolic coatings to reduce adhesion and biofilm formation of C. albicans BWP17 on titanium implants. Tannic acid and pyrogallol coatings altered the hydrophobic and charge properties of titanium surfaces, and both compounds were gradually released as active molecules over time. Despite such effects, we found no significant inhibition on growth and biofilm formation of C. Albicans, indicating that the release of active molecules from the coatings did not reach relevant inhibitory concentrations. However, a potential antibiofilm effect was observed by the pH-dependent disassembly of the polyphenolic layer, which caused the biofilm to detach. Hence, further efforts are required to create tailored implant surfaces, which sustainably reduce microbial growth and adhesion.

Oral candidiasis and denture stomatitis in diabetic patients: Systematic review and meta-analysis.

Here, the prevalence of oral candidiasis and denture stomatitis among diabetic patients compared to healthy ones was summarized through a systematic review with meta-analysis. Medline, Scopus, Web of Science, Lilacs, Cochrane Library, Embase, and the grey literature were searched without restriction, until May 2020. Eligibility criteria were established, data were extracted, and quality assessment was conducted by two trained examiners. Qualitative synthesis was based on the recommendations of Fowkes and Fulton. Two meta-analyses were performed on studies investigating patients with: a) oral candidiasis and b) denture stomatitis. Out of 6034 screened studies, seven were eligible for qualitative and quantitative synthesis; of these, three evaluated oral candidiasis and four evaluated denture stomatitis. Qualitative synthesis showed that the main methodological problems of the studies included sample size, source of controls, matching, and randomization. Diabetic patients had a similar chance of developing oral candidiasis to non-diabetic patients (OR1.40 [0.96; 2.04], p = 0.08, I2 = 94%). However, diabetic patients had a higher chance to present denture stomatitis compared to non-diabetic patients (OR 1.92 [1.42, 2.59] p < 0.0001, I2 = 0%). Therefore, diabetic patients have a higher chance of developing denture stomatitis compared to non-diabetic patients. However, for all analyses, the certainty of the evidence was considered to be very low.

Glucose effect on Candida albicans biofilm during tissue invasion.

OBJECTIVE: To evaluate, in vitro, the effect of two glucose concentrations (0.1 mM and 1.0 mM, simulating glucose concentration in saliva of healthy and diabetic individuals) on Candida albicans biofilm grown on epithelial monolayer. MATERIAL AND METHODS: C. albicans was inoculated on epithelial monolayers supplemented with 0.1 mM, 1.0 mM or no glucose. Control groups without C. albicans were also evaluated. Tissue response was assessed through the production of Interleukin-1α, Interleukin-8, Interleukin-6, Interleukin-10 and tumor necrosis factor-α. The complex of monolayer and biofilms were evaluated by quantitative reverse transcription polymerase chain reaction for expression of E-cadherin (CDH1), Caspase-3 (CASP3), ß-defensin-1 (DEFB-1) and ß-defensin-3 (DEFB-3). The biofilm architecture was visualized by confocal laser scanning microscopy. RESULTS: The production of Interleukin-1α and Interleukin-8 were increased in the presence of C. albicans (p < 0.05). Glucose did not interfere in the release of any cytokine evaluated. C. albicans downregulated transcripts for CDH1 (p < 0.05). Glucose did not induce a significant change in CDH1, CASP3, DEFB-1 and DEFB-3 messenger RNA expression. The biofilms were more structured in the presence of glucose, but no difference in the diffusion of hyphae through the epithelial cells were observed. CONCLUSIONS: The data suggest that glucose concentration does not affect the behavior of C. albicans during tissue invasion and other mechanisms must be related to the greater susceptibility of diabetic individuals to candidiasis.

Oral candidiasis and denture stomatitis in diabetic patients: Systematic review and meta-analysis

Abstract Here, the prevalence of oral candidiasis and denture stomatitis among diabetic patients compared to healthy ones was summarized through a systematic review with meta-analysis. Medline, Scopus, Web of Science, Lilacs, Cochrane Library, Embase, and the grey literature were searched without restriction, until May 2020. Eligibility criteria were established, data were extracted, and quality assessment was conducted by two trained examiners. Qualitative synthesis was based on the recommendations of Fowkes and Fulton. Two meta-analyses were performed on studies investigating patients with: a) oral candidiasis and b) denture stomatitis. Out of 6034 screened studies, seven were eligible for qualitative and quantitative synthesis; of these, three evaluated oral candidiasis and four evaluated denture stomatitis. Qualitative synthesis showed that the main methodological problems of the studies included sample size, source of controls, matching, and randomization. Diabetic patients had a similar chance of developing oral candidiasis to non-diabetic patients (OR1.40 [0.96; 2.04], p = 0.08, I2 = 94%). However, diabetic patients had a higher chance to present denture stomatitis compared to non-diabetic patients (OR 1.92 [1.42, 2.59] p < 0.0001, I2 = 0%). Therefore, diabetic patients have a higher chance of developing denture stomatitis compared to non-diabetic patients. However, for all analyses, the certainty of the evidence was considered to be very low.