Powder diet exacerbates oropharyngeal candidiasis in a mouse model.

This study reports on the influence of a powder diet in a mouse model of oropharyngeal candidiasis (OPC), a significant health concern caused primarily by Candida albicans. Despite identical nutritional composition, we found that a powdered diet significantly increased Candida burdens and oral lesions, and aggravated weight loss compared to a standard pelleted diet. High fungal burdens and severe oral lesions were accomplished within 48 hours after infection with only one dose of cortisone. Moreover, mice on a powder diet recovered a week after infection. Using a powder diet, we thus modified the cortisone OPC murine model in a way that simplifies the infection process, enhances reproducibility, and facilitates studies investigating both pathogenesis and recovery processes. Our findings also underscore the pivotal role of the physical form of the diet in the progression and severity of oral Candida infection in this model. Future research should investigate this relationship further to broaden our understanding of the underlying mechanisms, potentially leading to novel prevention strategies and improved disease management.IMPORTANCEOropharyngeal candidiasis (OPC) is a multifactorial disease and a significant health concern. We found that the physical form of the diet plays a critical role in the severity and progression of OPC. We developed a modified cortisone OPC murine model that facilitates studies investigating pathogenesis and recovery processes.

Curcuminoid-Mediated Antimicrobial Photodynamic Therapy on a Murine Model of Oral Candidiasis.

Antimicrobial Photodynamic Therapy (aPDT) has been extensively investigated in vitro, and preclinical animal models of infections are suitable for evaluating alternative treatments prior to clinical trials. This study describes the efficacy of aPDT in a murine model of oral candidiasis. Forty mice were immunosuppressed with subcutaneous injections of prednisolone, and their tongues were inoculated using an oral swab previously soaked in a C. albicans cell suspension. Tetracycline was administered via drinking water during the course of the experiment. Five days after fungal inoculation, mice were randomly distributed into eight groups; a ninth group of untreated uninfected mice was included as a negative control (n = 5). Three concentrations (20 µM, 40 µM, and 80 µM) of a mixture of curcuminoids were tested with a blue LED light (89.2 mW/cm2; ~455 nm) and without light (C+L+ and C+L- groups, respectively). Light alone (C-L+), no treatment (C-L-), and animals without infection were evaluated as controls. Data were analyzed using Welch's ANOVA and Games-Howell tests (α = 0.05). Oral candidiasis was established in all infected animals and visualized macroscopically through the presence of characteristic white patches or pseudomembranes on the dorsum of the tongues. Histopathological sections confirmed a large presence of yeast and filaments limited to the keratinized layer of the epithelium in the C-L- group, and the presence of fungal cells was visually decreased in the images obtained from mice subjected to aPDT with either 40 µM or 80 µM curcuminoids. aPDT mediated by 80 µM curcuminoids promoted a 2.47 log10 reduction in colony counts in comparison to those in the C-L- group (p = 0.008). All other groups showed no statistically significant reduction in the number of colonies, including photosensitizer (C+L-) or light alone (C-L+) groups. Curcuminoid-mediated aPDT reduced the fungal load from the tongues of mice.

The profile of chronic hyperplastic candidiasis: a clinico-pathological study.

The aims of this study were investigation of clinical presentation, systemic factors, and long-term malignant transformation rate in chronic hyperplastic candidiasis versus leukoplakia. This is a retrospective case-controlled study of cases with chronic hyperplastic candidiasis and leukoplakia without dysplasia, diagnosed between 2000 and 2013. A database was created, and all additional biopsies from the same cases were searched up to 2022, for records of oral malignant transformation. Associations between microscopic diagnoses and clinical features of lesions and clinical outcomes of patients were performed. A study database included 116 patients, allocated to the group diagnosed with chronic hyperplastic candidiasis (CHC-group, 62) and to the group of leukoplakia without dysplasia (LKP-group, 54). Tongue and buccal mucosa were most frequently recorded in both groups. In CHC-group, significantly fewer cases presented as white lesions compared to LKP-group (P < 0.001); more were ulcerated or exophytic (P = 0.006 and P = 0.003, respectively). History of head and neck malignancy was significantly more frequent in CHC-group (P = 0.005), as were chemotherapy, (P = 0.019) radiotherapy (P = 0.0265), and immune-related conditions (P = 0.03). Within the follow-up period (2000-2022), in CHC-group, two cases (3.2%) had malignant transformation at the site of original biopsy, one was recurrence of previous carcinoma. In LKP-group, two cases (3.7%) had newly diagnosed carcinoma and one at the site of original biopsy; no significant differences were found between groups. In conclusion, medical background of immune-related conditions, head and neck malignancy, radiotherapy, and chemotherapy may play a role in predisposing for chronic hyperplastic candidiasis. Malignant transformation rate within CHC-group was low, and similar to that within LKP-group, representing a lower transformation rate than expected.

Oral candidiasis and seborrheic dermatitis in an 8-year-old female with a heterozygous variant of the IL-17RC gene.

An 8-year-old female with chronic oral candidiasis and severe seborrheic dermatitis was found to have a heterozygous mutation (p.R14X c.40 C>T) of the IL-17RC gene, which was predicted to possibly represent a new pathogenic variant via truncation or nonsense-mediated mRNA decay. Given previously reported IL-17RC-related disorders are autosomal recessive, we would expect an affected individual to have two mutated alleles whereas our patient was heterozygous. Given the overlapping clinical picture, this variant could be responsible for altered immunity against both Candida and Malassezia species. This is the first report to our knowledge of chronic oral candidiasis and severe seborrheic dermatitis in a patient with a heterozygous variant (p.R14X c.40 C>T) for the IL-17RC gene.

Understanding the Protective Role of IL-17 During Oropharyngeal Candidiasis.

Oropharyngeal candidiasis is an opportunistic mucosal infection caused predominantly by Candida albicans. While healthy individuals are protected, susceptibility is associated with immunodeficiency. In particular, patients with defects related to T helper-17 (Th17) cells and interleukin (IL)-17 signaling are highly susceptible to mucocutaneous forms of candidiasis. Since mice are naïve to Candida albicans, induction of oropharyngeal candidiasis enables a thorough understanding of IL-17 and its related immune components during acute infection. Here we describe a murine model of oropharyngeal candidiasis. This protocol allows for translatable and reproducible infection with results that can be obtained between 2 and 5 days following infection.

Expression Profiles of GILZ and Annexin A1 in Human Oral Candidiasis and Lichen Planus.

Adrenal glands are the major source of glucocorticoids, but recent studies indicate tissue-specific production of cortisol, including that in the oral mucosa. Both endogenous and exogenous glucocorticoids regulate the production of several proteins, including the glucocorticoid-induced leucine zipper (GILZ) and Annexin A1, which play important roles in the regulation of immune and inflammatory responses. Common inflammation-associated oral conditions include lichen planus and candidiasis, but the status of GILZ and Annexin A1 in these human conditions remains to be established. Accordingly, archived paraffin-embedded biopsy samples were subjected to immunohistochemistry to establish tissue localization and profile of GILZ and Annexin A1 coupled with the use of hematoxylin-eosin stain for histopathological assessment; for comparison, fibroma specimens served as controls. Histopathological examination confirmed the presence of spores and pseudohyphae for oral candidiasis (OC) specimens and marked inflammatory cell infiltrates for both OC and oral lichen planus (OLP) specimens compared to control specimens. All specimens displayed consistent and prominent nuclear staining for GILZ throughout the full thickness of the epithelium and, to varying extent, for inflammatory infiltrates and stromal cells. On the other hand, a heterogeneous pattern of nuclear, cytoplasmic, and cell membrane staining was observed for Annexin A1 for all specimens in the suprabasal layers of epithelium and, to varying extent, for inflammatory and stromal cells. Semi-quantitative analyses indicated generally similar fractional areas of staining for both GILZ and Annexin A1 among the groups, but normalized staining for GILZ, but not Annexin A1, was reduced for OC and OLP compared to the control specimens. Thus, while the cellular expression pattern of GILZ and Annexin A1 does not differentiate among these conditions, differential cellular profiles for GILZ vs. Annexin A1 are suggestive of their distinct physiological functions in the oral mucosa.

Experimental animal models for denture stomatitis: A methodological review.

Denture stomatitis is the most prevalent form of oral candidiasis and the most frequent oral lesion in removable prosthesis wearers. It is characterized by an inflammatory response of the denture-bearing mucosa, especially the palatal mucosa, and its clinical signs include chronic edema and erythema, and papillary hyperplasia. Despite having a multifactorial etiology, its main etiological agent is the infection by Candida albicans. Given its high treatment failure rates, an in vivo model of denture stomatitis should be established to test alternative treatments. The aim of this study is to review the existing denture stomatitis models and to provide an overview of the main methodological differences between them. Over the last 40 years, different animal models were developed in order to study denture stomatitis etiopathogenesis and to assess novel therapies. Many approaches, including the use of antibiotics and immunosuppressors, have to be further investigated in order to establish which protocol is more appropriate and effective for the development of an animal model of denture stomatitis.

Pseudomembranous oral candidiasis resolved with a mouthwash containing 0.05% chlorhexidine + 0.05% cetylpyridinium chloride.

A 50-year-old woman was referred to the clinic reporting oral discomfort during the previous month and plaques of a white removable slough. Diagnosis of pseudomembranous oral candidiasis was clinically confirmed. When the tongue and palatal mucosa were wiped with gauze, the soft yellowish-white slough detached revealing the erythematous surface beneath. The patient also presented paranoid schizophrenia and severe depression, pulmonary emphysema, and two vertebral hernias. She was a smoker (10 cigarettes per day) with xerostomia that was being treated with: bupropion, reboxetine, quetiapine, trazadone clotiapine, pregabalin, fentanyl (patches), and alprazolam. To minimize the risk of potential drug interactions, a mouthwash containing 0.05% chlorhexidine + 0.05% cetylpyridinium chloride was prescribed three times a day for two weeks. At the end of the two weeks, the candidiasis had abated.

Activation of EphA2-EGFR signaling in oral epithelial cells by Candida albicans virulence factors.

During oropharyngeal candidiasis (OPC), Candida albicans invades and damages oral epithelial cells, which respond by producing proinflammatory mediators that recruit phagocytes to foci of infection. The ephrin type-A receptor 2 (EphA2) detects ß-glucan and plays a central role in stimulating epithelial cells to release proinflammatory mediators during OPC. The epidermal growth factor receptor (EGFR) also interacts with C. albicans and is known to be activated by the Als3 adhesin/invasin and the candidalysin pore-forming toxin. Here, we investigated the interactions among EphA2, EGFR, Als3 and candidalysin during OPC. We found that EGFR and EphA2 constitutively associate with each other as part of a heteromeric physical complex and are mutually dependent for C. albicans-induced activation. Als3-mediated endocytosis of a C. albicans hypha leads to the formation of an endocytic vacuole where candidalysin accumulates at high concentration. Thus, Als3 potentiates targeting of candidalysin, and both Als3 and candidalysin are required for C. albicans to cause maximal damage to oral epithelial cells, sustain activation of EphA2 and EGFR, and stimulate pro-inflammatory cytokine and chemokine secretion. In the mouse model of OPC, C. albicans-induced production of CXCL1/KC and CCL20 is dependent on the presence of candidalysin and EGFR, but independent of Als3. The production of IL-1α and IL-17A also requires candidalysin but is independent of Als3 and EGFR. The production of TNFα requires Als1, Als3, and candidalysin. Collectively, these results delineate the complex interplay among host cell receptors EphA2 and EGFR and C. albicans virulence factors Als1, Als3 and candidalysin during the induction of OPC and the resulting oral inflammatory response.

Candida albicans Interaction with Oral Epithelial Cells: Adhesion , Invasion, and Damage Assays.

Microbial interactions with epithelial barriers are important steps preceding disease. Infections with Candida albicans are no exception. This opportunistic fungus, commonly harmlessly residing in close proximity to human epithelia, can shift to a more pathogenic form, can invade tissues, and cause disease. Pathogenesis, in C. albicans as well as in many other microorganisms, is characterized by three important steps: adhesion to-, invasion into-, and damage of host cells. In this book chapter, we describe three well-established protocols that allow us to differentially stain C. albicans cells adhering to and invading into host cells, therefore allowing quantifications of such processes. We also describe a common host cell cytotoxicity assay that employs a commercial kit, adapted to C. albicans.

Histopathologic aspects of the so-called chronic hyperplastic candidiasis: An analysis of 36 cases.

BACKGROUND: The present study aimed to analyze the histopathologic aspects of cases diagnosed as chronic hyperplastic candidiasis (CHC) in an oral pathology service, pointing out the most important features found. METHODS: All cases histopathologically diagnosed as CHC between 2002 and 2018 were retrieved from the files of the service. Data of the patients and the lesions were collected. Histopathological analysis was performed to evaluate the microscopic characteristics and the amount of Candida present. RESULTS: Thirty-six cases of CHC were retrieved. Women were more affected and there was a predilection for Whites. Most lesions appeared as a nodule or a white plaque, asymptomatic, on the tongue or buccal mucosa. Histopathologically, statistical significance was noted for the presence of epithelial hyperplasia, exocytosis, and mononuclear inflammatory infiltrate. Interestingly, only the association between dysplasia and the amount of fungus was noted. CONCLUSIONS: CHC appears to be a distinct entity presenting typical histopathologic aspects. CHC might even show epithelial dysplasia. In those cases, the presence of a large amount of Candida together with other histopathological features should lead to the diagnosis of CHC and subsequent treatment. However, close follow up is important.

Atividade antifúngica e potencial antibiofiome do extrato hidroetanólico de Spondias mombin L. e de suas frações frente a leveduras do gênero Candida / Antifungal activity and antibiofiome potential of the hydroethanolic extract of Spondias mombin L. and its fractions against yeasts of the genus Candida

A Candidose é uma patologia que pode ter manifestações locais e também sistêmicas e acontece pela proliferação de fungos do gênero Candida. O tratamento desta patologia é realizado com antifúngicos mas, devido a resistência dos fungos causadores desta enfermidade se faz necessário conhecer outros antifúngicos. A ação antimicrobiana do extrato hidroetanólico de Spondias mombin L. já é conhecida e é fundamental que seja pesquisado a atividade antibiofilme das substâncias, uma vez que estes fungos causam adoecimento quando se acumulam e proliferam. Sabendo disso é que o presente estudo teve por objetivo principal investigar a ação antifúngica e antibiofilme do extrato hidroetanólico (EH) de Spondias mombin L. e das frações de taninos, flavonoides e ácidos fenólicos, frente a fungos do gênero Candida, de importância clínica. Para isto, determinou-se a concentração inibitória mínima por meio do uso de discos e pela técnica da microdiluição em caldo, concentração inibitória mínima de aderência, determinação da curva de morte dos fungos e atividade antibiofilme das frações de ácidos fenólicos, flavonoides e tanino, frente aos fungos Candida albicans, Candida tropicalis, Candida Krusei e Candida Glabrata, utilizando como controle positivo a Nistatina (100.000 UI), em triplicata. Foi visto que, a atividade antifúngica e antibiofilme do EH e de suas frações analisadas existe, porém, quando comparamos as frações com o EH este último apresentou melhor atividade em suas maiores concentrações (500 µg/mL e 250 µg/mL) e quando traçamos o comparativo entre a ação antifúngica e antibiofilme das substâncias testadas e do grupo controle, tivemos melhores resultados do grupo controle frente aos fungos testados. Desta forma foi possível concluir que o extrato hidroetanólico apresentam resultados superiores de atividade antifúngica frente a todos os microrganismos testados, exceto C. krusei e antibiofilme frente a, pelo menos, uma das espécies de Candida e que este extrato teve resultados muito semelhantes e, por vezes, superior ao grupo controle (AU).

Candidosis is a pathology that can have local as well as systemic manifestations and happens due to the proliferation of fungi of the Candida genus. The treatment of this pathology is carried out with antifungal agents, but due to the resistance of the fungi that cause this disease, it is necessary to know other antifungal agents. The antimicrobial action of the hydroethanolic extract of Spondias mombin L. is already known and it is essential that the antibiofilm activity of the substances be researched, since these fungi cause illness when they accumulate and proliferate. Knowing that, this study aimed to investigate the antifungal and antibiofilm action of the hydroethanolic extract (EH) of Spondias mombin L. and its fractions, against fungi of the genus Candida, of clinical importance. For this, the minimum inhibitory concentration was determined through the use of disks and the technique of microdilution in broth, minimum inhibitory concentration of adhesion, determination of the fungal death curve and antibiofilm activity of the fractions of phenolic acids, flavonoids and tannin, against the fungi Candida albicans, Candida tropicalis, Candida Krusei and Candida Glabrata, using nystatin (100,000 IU) as a positive control, in triplicate. It was seen that the antifungal and antibiofilm activity of EH and its analyzed fractions exists, however, when we compare the fractions with EH, the latter showed better activity at its highest concentrations (500 µg/mL e 250 µg/mL) and when we draw the comparison between the antifungal and antibiofilm action of the tested substances and the control group, we had better results than the control group against the tested fungi. Thus, it was possible to conclude that the hydroethanolic extract presented superior results of antifungal activity against all tested microorganisms, except C. krusei and antibiofilm against at least one of the Candida species and that this extract had very similar results and, for times higher than the control group (AU).

Hyposalivation, oral health, and Candida colonization in independent dentate elders.

Hyposalivation is an important problem in elders and could interfere with several oral functions and microbial ecology. While the number of independent elders who retain more natural teeth increases worldwide, few studies examined hyposalivation in this population. Thus, this study aims to examine relationships between hyposalivation, oral health conditions and oral Candida colonization in independent dentate elders and evaluate factors associated with salivary flow and Candida carriage. We conducted a cross-sectional study in fifty-three dentate elders (≥65 years old with at least 4 pairs of posterior occlusal contacts) with no, or well-controlled, systemic conditions. Participants were interviewed for medical history, subjective dry mouth symptoms, oral hygiene practices and denture information. Unstimulated and stimulated salivary flow rates, objective dry mouth signs, gingival, tongue-coating, and root-caries indices were recorded. Stimulated saliva was cultured on Sabouraud-dextrose agar for Candida counts. Candida species were identified using chromogenic Candida agar and polymerase chain reaction. Statistical significance level was set at p<0.05. The results showed that hyposalivation was associated with higher gingival and tongue-coating indices (p = 0.003 and 0.015, respectively), but not root-caries index. Hyposalivation was also associated with higher prevalence of oral Candida colonization (p = 0.010; adjusted OR = 4.36, 95% confidence interval = 1.29-14.72). These two indices and Candida load were negatively correlated with unstimulated and stimulated salivary flow rates. Interestingly, non-albicans Candida species were more prevalent in denture wearers (p = 0.017). Hence, hyposalivation is a risk factor for poorer oral health and oral Candida colonization in independent dentate elders. Because of its potential adverse effects on oral and systemic health, hyposalivation should be carefully monitored in elders.

First neonates with severe acute respiratory syndrome coronavirus 2 infection in Romania: Three case reports.

RATIONALE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which quickly spread throughout the world, has been putting medical workers all over the world in difficulty because of the high number of cases combined with the lack of information about the disease. Although pediatric cases are rare, the group age under 12 months has been in general more susceptible to develop severe forms of the disease compared with the patients in the age interval of 1 to 18 years. PATIENT CONCERNS: Three newborns have been tested positive for SARS-CoV-2 infection. One of them presented bilateral decreased air entry, while the other 2 had no respiratory symptomatology. All 3 developed diaper erythema and oral candidiasis. DIAGNOSIS: For building up the report, newborns that were positive for coronavirus disease 2019 (COVID-19) infection were included in the case series. The chest X-ray of the symptomatic patient revealed a medium degree of hilar parenchymal infiltration and a slight infiltration of the visceral pleura. INTERVENTIONS: The patients were admitted in our isolated neonatology ward. All of them received antifungal treatment for the oral candidiasis and topic cream for diaper erythema. The symptomatic patient also received prophylactic antibiotherapy, human immunoglobulins, aminophylline, and parenteral nutrition. OUTCOMES: All 3 neonates were discharged after 2 consecutive negative tests for SARS-CoV-2. Patients 1 and 2 fully recovered, whereas the condition of patient 3 improved. LESSONS: Even if there are only a few reported cases of neonates infected with COVID-19 and most of them present mild manifestations, newborns need a more careful insight because of the nonspecific symptomatology.

Perillaldehyde: A promising antifungal agent to treat oropharyngeal candidiasis.

Perillaldehyde (PAE), a natural monoterpenoid agent extracted from Perilla frutescence, PAE has been reported to present various physiological capabilities, such as anti-inflammation, anti-oxidative and anti-fungal. In this study, we show that PAE exhibits strong antifungal activity against Candida albicans (C. albicans). C. albicans, a fungal pathogen with high incidence of antifungal resistance in clinical settings, is the major cause of oropharyngeal candidiasis (OPC). OPC is characterized by inflammatory immunological responses to fungal infections. Our in vitro results show PAE inhibited several virulence attributes of C. albicans including biofilm formation, yeast-to-hyphal transition and secreted aspartic proteinases (SAPs) gene expression. Using an experimental murine model of OPC, we found that PAE inhibited NLRP3 inflammasome assembly, reduced the excessive accumulation of ROS and prevented the p65 transfer in nuclear; processes all leading to reduced inflammation burden in the host. Together, this supports use PAE as a promising new agent to improve OPC.

Effect of probiotic bacteria on oral Candida in head- and neck-radiotherapy patients: A randomized clinical trial.

OBJECTIVE: The aim of the study is to assess the effect of probiotic bacteria on oral Candida counts in cancer patients who are undergoing head- and neck-radiotherapy in a tertiary care center. STUDY DESIGN: The study was a randomized clinical trial including 90 patients who just completed head- and neck-radiotherapy. MATERIALS AND METHODS: Participants were randomly allocated into three equal sized groups, i.e., probiotics group, candid group, and combination groups. Oral rinse samples of the patients were collected before and after the intervention for the identification of Candida. The samples were incubated on Sabouraud's Dextrose Agar with Chloramphenicol at 37°C for 48 h, to assess the counts of colony-forming units/milliliter (CFU/ml) of Candida in saliva, and further on chrome agar plates to identify the Candida spp. Data were analyzed using mixed ANOVA to compare mean CFU/ml of Candida among three groups before and after the intervention. RESULTS: A total of 86 patients were included in the final analysis and there was a statistically significant reduction in mean Candida spp. Counts (CFU/ml) after intervention in all the three groups (P = 0.000) and significant reductions identified in both probiotic and combination therapy groups. Apart from reduction in Candida albicans, significant decrease in Candida glabrata and Candida tropicalis was observed after probiotics usage compared to other groups. CONCLUSIONS: The present study suggests that probiotic bacteria were effective in reducing oral Candida spp which can be recommended alone or in combination with traditional antifungal agents for effective reduction in oral Candida in head- and neck-radiotherapy patients.

The Interleukin (IL) 17R/IL-22R Signaling Axis Is Dispensable for Vulvovaginal Candidiasis Regardless of Estrogen Status.

Candida albicans, a ubiquitous commensal fungus that colonizes human mucosal tissues and skin, can become pathogenic, clinically manifesting most commonly as oropharyngeal candidiasis and vulvovaginal candidiasis (VVC). Studies in mice and humans convincingly show that T-helper 17 (Th17)/interleukin 17 (IL-17)-driven immunity is essential to control oral and dermal candidiasis. However, the role of the IL-17 pathway during VVC remains controversial, with conflicting reports from human data and mouse models. Like others, we observed induction of a strong IL-17-related gene signature in the vagina during estrogen-dependent murine VVC. As estrogen increases susceptibility to vaginal colonization and resulting immunopathology, we asked whether estrogen use in the standard VVC model masks a role for the Th17/IL-17 axis. We demonstrate that mice lacking IL-17RA, Act1, or interleukin 22 showed no evidence for altered VVC susceptibility or immunopathology, regardless of estrogen administration. Hence, these data support the emerging consensus that Th17/IL-17 axis signaling is dispensable for the immunopathogenesis of VVC.

Potential role of Candida albicans secreted aspartic protease 9 in serum induced-hyphal formation and interaction with oral epithelial cells.

INTRODUCTION: Candida albicans possesses the ability to switch rapidly between yeast to hyphal forms. Hyphal formation is a remarkable pathogenic characteristic, which allows C. albicans to invade into host cells. OBJECTIVES: This study was to investigate the role of the C. albicans SAP9 gene in hyphal formation and invasion ability. METHODS: The morphology of fungal cells in the hyphal-inducing liquid media (YPD+10% fetal bovine serum) was observed by the microscopy. And the morphology of the colony on solid agar plates of YPD+10% fetal bovine serum was photographed by the digital camera. The mRNA expressions of hypha-associated genes in serum medium were also analyzed by real time PCR. Then for the interaction between C. albicans and oral epithelial cells, endocytosis essay, invasion essay and damage assay were performed to compare the differences between the sap9Δ/Δ mutant strain and wild type strain. RESULTS: Compared with the wild type strain, the sap9Δ/Δ mutant strain exhibited a deficient yeast-to-hyphal morphological transition under serum hyphal-inducing conditions. Furthermore, the SAP9 knockout strain revealed a significant down-regulation of the expression of EFG1 (~40%), which is a transcription factor gene that mediates hyphae formation in C. albicans. Compared with the wild type strain, a 70% reduction in the endocytosis of the sap9Δ/Δ mutant strain by host cells was observed, as well as a 25% attenuation of active penetration and a 40% attenuation of host cell damage (P <0.05). CONCLUSIONS: Our data strongly suggests that C. albicans Sap9 is a potential hyphal-associated factor that responds to serum hyphal-inducing stimuli via a cAMP-protein kinase A pathway mediated by EFG1, and contributes to the process of invasion of Candida into the epithelial cells, leading to host cell damage.

Identification and Antifungal Activity Profile of Candida Species Isolated from Patients with Pemphigus Vulgaris with Oral Lesions.

Pemphigus vulgaris is an autoimmune disease that mostly affects the mucosa and oral cavity. Candida species can invade the mucosal lesions of these patients and cause diseases. The aim of this study was to identify the fungal agents isolated from mucosal lesions and evaluate antifungal activity profile against the isolates. A total of 25 patients with pemphigus vulgaris with active oral lesions and 25 healthy people serving as a control group were included in this study. Identification of the fungal isolates was performed based on conventional methods and DNA sequence analysis of the internal transcribed spacer (ITS) rDNA gene region. The sequence results were deposited in the NCBI database using the Basic Local Alignment Search Tool. Antifungal activity of fluconazole, itraconazole, ketoconazole, posaconazole, econazole, and amphotericin B against the isolates were evaluated based on the CLSI M-44 A protocol. Oral candidiasis was detected in 20% of the patients. Candida species isolated from oral lesions of patients with pemphigus were identified as Candida albicans 22/25, Candida glabrata 2/25, and Candida dubliniensis 1/25. All of the isolates were sensitive to amphotericin and econazole, 96% to fluconazole and posaconazole, and 92% to ketoconazole and itraconazole. One patient showed a profile resistant to fluconazole, posaconazole, and ketoconazole, simultaneously. Ninety six percent of control group isolates were sensitive to six antifungals. Candida albicans was the most prevalent species isolated from oral lesions of patients with pemphigus vulgaris and the control group. Amphotericin B and econazole were the most effective antifungals against the isolates.

Candidiasis Causing Vocal Fold Leukoplakia: Review of Clinical and Pathological Results of 289 Cases With Vocal Fold Leukoplakia.

OBJECTIVE: In laryngology practice, vocal fold leukoplakia is frequently evaluated by suspension laryngoscopy and biopsy examination upon the patient's complaints of hoarseness and dysphonia. The purpose of the present study is to investigate and analyze risk factors, diagnosis, treatment, and follow-up results of cases with Candida leukoplakia. STUDY DESIGN: Retrospective case control study. SETTING: Tertiary medical center. SUBJECTS AND METHODS: Patients with a diagnosis of vocal fold leukoplakia who underwent direct laryngoscopy and biopsy between 2007 and 2017 and diagnosed as candida or noncandida in their histopathology were assigned into 2 groups. Then they were compared in terms of their demographic characteristics, predisposing factors, diagnosis, treatment, and follow-up results. RESULTS: Of the 289 vocal fold leukoplakia cases, 36 were candida, and 253 were noncandida. The mean age of the patients with Candida leukoplakia was 60.86 years. As for the age groups, the largest group (26.1%) was in the seventh decade (P < .001). The use of inhaled corticosteroids was a significant risk factor (P < .001). For their medical therapy, the patients were administered fluconazole 200 mg per day for 3 weeks, and the treatment yielded successful results in 91.66% of them. In 5 of the patients, candida leukoplakia and superficial epithelial dysplasia were observed, and no malignant transformation was observed during a mean follow-up of 28 ± 13 months. CONCLUSION: Candidiasis causing vocal fold leukoplakia is rare, and we report the findings of the largest published case series to date. Eliminating predisposing factors and administrating oral fluconazole 200 mg for 3 weeks are sufficient for medical treatment.