The ability of Candida albicans to invade mucosal tissues is a major virulence determinant of this organism; however, the mechanism of invasion is not understood in detail. Proteolytic breakdown of E-cadherin, the major protein in epithelial cell junctions, has been proposed as a mechanism of invasion of certain bacteria in the oral mucosa. The objectives of this study were (i) to assess whether C. albicans degrades E-cadherin expressed by oral epithelial cells in vitro; (ii) to compare the abilities of strains with different invasive potentials to degrade this protein; and (iii) to investigate fungal virulence factors responsible for E-cadherin degradation. We found that while E-cadherin gene expression was not altered, E-cadherin was proteolytically degraded during the interaction of oral epithelial cells with C. albicans . Moreover, C. albicans -mediated degradation of E-cadherin was completely inhibited in the presence of protease inhibitors. Using a three-dimensional model of the human oral mucosa, we found that E-cadherin was degraded in localized areas of tissue invasion by C. albicans . An invasion-deficient rim101 ⁻ / rim101 ⁻ strain was deficient in degradation of E-cadherin, and this finding suggested that proteases may depend on Rim101p for expression. Indeed, reverse transcription-PCR data indicated that expression of the SAP4 , SAP5 , and SAP6 genes is severely reduced in the rim101 ⁻ / rim101 ⁻ mutant. These SAP genes are functional Rim101p targets, because engineered expression of SAP5 in the rim101 ⁻ / rim101 ⁻ strain restored E-cadherin degradation and invasion in the mucosal model. Our data support the hypothesis that there is a mechanism by which C. albicans invades mucosal tissues by promoting the proteolytic degradation of E-cadherin in epithelial adherens junctions.

The oral cavity presents a highly diverse community of microorganisms due to the unique environmental conditions for microbial adhesion and growth

Candida albicansis a major opportunistic pathogen in immunocompromised patients. Production of proinflammatory cytokines by host cells in response toC. albicansplays a critical role in the activation of immune cells and final clearance of the organism. Invasion of host cells and tissues is considered one of the virulence attributes of this organism. The purpose of this study was to investigate whether the ability ofC. albicansto invade host cells and tissues affects the proinflammatory cytokine responses by epithelial and endothelial cells. In this study we used the invasion-deficientRIM101gene knockout strain DAY25, the highly invasive strain SC5314, and highly invasiveRIM101-complemented strain DAY44 to compare the proinflammatory cytokine responses by oral epithelial or endothelial cells. Using a high-throughput approach, we found both qualitative and quantitative differences in the overall inflammatory responses toC. albicansstrains with different invasive potentials. Overall, the highly invasive strains triggered higher levels of proinflammatory cytokines in host cells than the invasion-deficient mutant triggered. Significant differences compared to the attenuated mutant were noted in interleukin-1α (IL-1α), IL-6, IL-8, and tumor necrosis factor alpha in epithelial cells and in IL-6, growth-related oncogene, IL-8, monocyte chemoattractant protein 1 (MCP-1), MCP-2, and granulocyte colony-stimulating factor in endothelial cells. Our results indicate that invasion of host cells and tissues byC. albicansenhances the host proinflammatory response to infection.

Background: Smoking is a major risk factor for periodontitis and tooth loss. Smoking cessation has a positive impact in periodontal treatment. However, so far, no systematic review has evaluated the effect of smoking cessation on tooth loss. Therefore, this review aimed to evaluate if smoking cessation reduces the risk of tooth loss. Methods: Observational (cross-sectional and longitudinal) studies that investigated the association between smoking cessation and tooth loss were included. MEDLINE, EMBASE and LILACS databases were searched for articles published up to November 2018. Pooled results for subgroups of current and former smokers were compared in meta-analysis. Meta-regression was used to test the influence of smoking status on estimates and explore the heterogeneity. Results: Of 230 potentially relevant publications, 21 studies were included in the qualitative review and 12 in the quantitative analysis. Meta-analysis of cross-sectional studies did not show any differences between former and current smokers in the chance of losing 1 or more teeth (OR = 1.00; 95% CI = 0.80 to 1.24, I² = 80%), losing more than 8 teeth (OR = 1.02; 95% CI = 0.78 to 1.32, I² = 0%) or being edentulous (OR = 1.37; 95% CI = 0.94 to 1.99, I² = 98%). Meta-analysis from longitudinal studies showed that, when compared to never smokers, former smokers presented no increased risk of tooth loss (RR = 1.15; 95% CI = 0.98 to 1.35, I² = 76%), while current smokers presented an increased risk of tooth loss (RR = 2.60; 95% CI = 2.29 to 2.96, I² = 61%). Meta-regression showed that, among former smokers, the time of cessation was the variable that better explained heterogeneity (approximately 60%). Conclusions: Risk for tooth loss in former smokers is comparable to that of never smokers. Moreover, former smokers have a reduced risk of tooth loss, when compared to current smokers.