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1.
PLoS Pathog ; 17(1): e1009221, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33471869

RESUMO

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.


Assuntos
Candida albicans/fisiologia , Candidíase Bucal/patologia , Efrina-A2/metabolismo , Células Epiteliais/patologia , Orofaringe/patologia , Fatores de Virulência/metabolismo , Animais , Candidíase Bucal/genética , Candidíase Bucal/metabolismo , Candidíase Bucal/microbiologia , Citocinas/metabolismo , Modelos Animais de Doenças , Efrina-A2/genética , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Orofaringe/metabolismo , Orofaringe/microbiologia , Fatores de Virulência/genética
2.
Methods Mol Biol ; 2260: 133-143, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33405035

RESUMO

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.


Assuntos
Candida albicans/patogenicidade , Candidíase Bucal/microbiologia , Adesão Celular , Células Epiteliais/microbiologia , Microscopia de Fluorescência , Mucosa Bucal/microbiologia , Candidíase Bucal/metabolismo , Candidíase Bucal/patologia , Linhagem Celular , Sobrevivência Celular , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Interações Hospedeiro-Patógeno , Humanos , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia
3.
Acta Odontol Latinoam ; 33(2): 104-111, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32920612

RESUMO

Candida dubliniensis (Cd) and Candida albicans (Ca) are the most frequently isolated yeasts in HIV+ patients. Some of the enzymes produced by these yeasts are considered virulence factors since they contribute to pathogenicity of Candida spp. The aim of the present study was to compare production of enzymes such as phospholipase (Ph), proteinase (P), and hemolysin (H) by Cd and Ca strains isolated from periodontal HIV-positive patients receiving and not receiving highly active antiretroviral therapy (HAART). Subgingival biofilm samples were obtained using paper points, and a sample of oral mucosa was taken using a swab. Phenotypic and molecular methods were used to isolate 39 strains of Candida, including 25 strains of Cd and 14 strains of Ca, obtained from 33 periodontal pocket samples and 6 oral mucosa samples collected from 15 HIV+ patients (8 receiving and 7 not receiving HAART). Malt egg-yolk agar, albumin agar and blood agar were used to evaluate pH, P and H production respectively. The strains were inoculated in duplicate and incubated at 37 ºC. Colony and halo diameters were measured. A greater proportion of Ca was observed in patients not receiving HAART, and a higher proportion of Cd was observed in those under HAART, Chi2 p< 0.001. Phospholipase production was observed in 92.9% percent of isolated Ca strains but in none of the isolated Cd strains. Proteinase production was high in Ca and Cd strains isolated from patients not receiving HAART. Hemolysin production was observed in all the studied strains, though it was significantly higher (p=0.04) in Ca and Cd strains isolated from patients not receiving HAART. To sum up, the proportion of Candida dubliniensis strains was highest in the subgingival biofilm of patients receiving HAART, and Cd strains were found to express fewer virulence factors than Ca strains.


Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , Biofilmes/crescimento & desenvolvimento , Candida albicans/enzimologia , Candida albicans/isolamento & purificação , Candida/enzimologia , Candida/isolamento & purificação , Candidíase Bucal/microbiologia , Gengiva/microbiologia , Infecções por HIV/complicações , Candida/classificação , Candida/genética , Candida albicans/genética , Candidíase Bucal/complicações , Genótipo , Infecções por HIV/microbiologia , Humanos , Mucosa Bucal/microbiologia , Fenótipo , Reação em Cadeia da Polimerase , Fatores de Virulência/genética
4.
J Mycol Med ; 30(3): 101009, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32620497

RESUMO

Chronic renal disease patients under chronic dialysis (CRDD) have a multifactorial immunological deterioration with an increased risk of Candida infections. Incidence of Candida infections is increasing. Choice of suitable antifungal agents is limited due to the resistance of some species to several antifungals. Aim of the present study was to identify the distribution and antifungal susceptibility patterns of oral isolated Candida species from infected and colonized patients, as well as to investigate the risk factors for oral infection in patients on dialysis. Cross-sectional study, approved by the institutional bioethics committees was performed in CRDD patients. Demographic, clinic data, and oral mucosa samples were obtained. Infection diagnosis was established clinically and confirmed with exfoliative cytology, each sample was plated on CHROMagar Candida and incubated at 36°C for 2 days. Yeast species were identified by carbohydrate assimilation ID 32C AUX system and the apiweb database. For the antifungal susceptibility test, the M44 A-3 method (CLSI) using fluconazole (FCZ), miconazole (MCZ), nystatin (NYS), and voriconazole (VCZ). Study included 119 participants, the main cause of CRD was nephropathy due to DM2 (58%), and three-fourths of the patients were under hemodialysis. Candida prevalence was 56.3% of 67 colonized or infected patients, 88 isolates were obtained. Principal identified species were C. albicans (51.1%), C. glabrata (25%), and C. tropicalis (14.8%). C. glabrata showed a reduced response to FCZ in 50% of isolates and C. albicans had a reduced response in 16% of the isolates. Antifungal agent with the least efficacious response or with the lowest susceptibility in the isolates of these patients was MCZ, followed by VCZ and FCZ, whereas NYS induced the best antifungal response.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candidíase Bucal/microbiologia , Boca/microbiologia , Insuficiência Renal Crônica/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Candida/classificação , Candidíase Bucal/complicações , Candidíase Bucal/diagnóstico , Candidíase Bucal/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/terapia , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/microbiologia , Nefropatias Diabéticas/terapia , Farmacorresistência Fúngica/efeitos dos fármacos , Feminino , Humanos , Masculino , México/epidemiologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Diálise Renal/estatística & dados numéricos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Adulto Jovem
5.
Mycoses ; 63(8): 771-778, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32609906

RESUMO

BACKGROUND: Emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. Apparently, the novel coronavirus (SARS-CoV-2) is armed by special abilities to spread and dysregulate the immune mechanisms. The likelihood of oropharyngeal candidiasis (OPC) development in COVID-19 patients with a list of attributable risk factors for oral infections has not yet been investigated. OBJECTIVES: We here aim to investigate the prevalence, causative agents and antifungal susceptibility pattern of OPC in Iranian COVID-19 patients. PATIENTS AND METHODS: A total of 53 hospitalised COVID-19 patients with OPC were studied. Relevant clinical data were mined. Strain identification was performed by 21-plex PCR and sequencing of the internal transcribed spacer region (ITS1-5.8S-ITS2). Antifungal susceptibility testing to fluconazole, itraconazole, voriconazole, amphotericin B, caspofungin, micafungin and anidulafungin was performed according to the CLSI broth dilution method. RESULTS: In 53 COVID-19 patients with OPC, cardiovascular diseases (52.83%) and diabetes (37.7%) were the principal underlying conditions. The most common risk factor was lymphopaenia (71%). In total, 65 Candida isolates causing OPC were recovered. C albicans (70.7%) was the most common, followed by C glabrata (10.7%), C dubliniensis (9.2%), C parapsilosis sensu stricto (4.6%), C tropicalis (3%) and Pichia kudriavzevii (=C krusei, 1.5%). Majority of the Candida isolates were susceptible to all three classes of antifungal drugs. CONCLUSION: Our data clarified some concerns regarding the occurrence of OPC in Iranian COVID-19 patients. Further studies should be conducted to design an appropriate prophylaxis programme and improve management of OPC in critically ill COVID-19 patients.


Assuntos
Antifúngicos/farmacologia , Candida/classificação , Candidíase Bucal/complicações , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Candida/efeitos dos fármacos , Candida/genética , Candidíase Bucal/microbiologia , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Irã (Geográfico) , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pandemias , Fenótipo , Pneumonia Viral/epidemiologia , Fatores de Tempo
6.
Epidemiol Health ; 42: e2020033, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32512666

RESUMO

Objectives: Oropharyngeal candidiasis is one of the most common opportunistic fungal infections among human immunodeficiency virus (HIV)-infected individuals. The most common cause is Candida albicans, followed by non-albicans Candida. This study aimed to identify colonized Candida species in HIV-infected patients from Ahvaz, Iran. Additionally, the relationships between immunity-related factors, lifestyle, and colonization of Candida spp. were studied. Methods: Oral swabs were taken from 201 HIV-positive patients referred for consultations at the Behavioral Modification Center. Oral Candida colonization was detected using culture-based and molecular assays. Data were assessed by descriptive statistics and analyzed to investigate the correlation between Candida colonization and various factors, including the CD4+ cell count and viral load. Results: It was found that 43.8% of patients were positive for Candida. The most common species was C. albicans (48.0%), followed by non-albicans Candida isolates, including C. dubliniensis, C. glabrata, C. tropicalis, C. parapsilosis, C. guilliermondii, C. kefyr, and C. krusei. Colonization of Candida spp. in patients was associated with a CD4 count ≤200 cells/mm3 (odds ratio [OR], 4.62; p<0.05), history of shared injections (OR, 6.96; p<0.001), and sex (OR, 3.59; p<0.05). Conclusions: The results of this study showed that C. albicans was the dominant pathogen. The risk factors for colonization of Candida spp. were a CD4 count ≤ 200/mm3 , a history of shared injections, and sex. Other factors with potential relationships include viral load, age, and opportunistic infections, but further investigations are needed.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Candida/isolamento & purificação , Candidíase Bucal/microbiologia , Infecções por HIV/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Candida albicans/isolamento & purificação , Candidíase Bucal/epidemiologia , Criança , Estudos Transversais , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
7.
BMC Oral Health ; 20(1): 72, 2020 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171292

RESUMO

BACKGROUND: The aim of this study was to investigate the prevalence and genotypic profiles of Candida albicans in patients with oral lichen planus (OLP). MATERIALS AND METHODS: Positive rates and genotypic profiles of Candida albicans strains from OLP patients and healthy controls were analyzed. Random amplified polymorphic DNA and internal transcribed spacer of ribosome DNA polymerase chain reactions were used to sequence the DNA of these strains, and then their genetic similarity was measured using BLAST, UIV Band, and Vector NTI Suite Sequence Analyses Software. RESULTS: The prevalence of C. albicans strains detected from erosive-OLP, non-erosive OLP, and normal individuals was 18.87, 18.75, and 7.92%, respectively. Four different genotypes were revealed by the two methods. To be specific, type I was found only in the healthy subjects; type II a and II b were found in non-erosive OLP, and type III was identified in erosive OLP. Intragroup similarity coefficients, i.e. SAB were 100%, and inter-groups similarity coefficients, i.e. SAB were less than 30%. CONCLUSIONS: The genotypic results of C. albicans in OLP revealed an endogenous rather than exogenous infection of C. albicans. In addition, a possible pathogenic role of C. albicans in OLP, with the etiologic sense contributing to a more proper recognition on the pathogenesis, development, and progression of OLP, as well as some strategies for its diagnosis and treatment were identified.


Assuntos
Candida albicans/genética , Candida albicans/patogenicidade , Candidíase Bucal/microbiologia , Líquen Plano Bucal/diagnóstico , Adulto , Idoso , Candida albicans/isolamento & purificação , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Líquen Plano Bucal/microbiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Técnica de Amplificação ao Acaso de DNA Polimórfico , Análise de Sequência de DNA
8.
Microb Pathog ; 139: 103896, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31794816

RESUMO

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.


Assuntos
Ácido Aspártico Endopeptidases/metabolismo , Candida albicans/fisiologia , Candidíase Bucal/metabolismo , Candidíase Bucal/microbiologia , Proteínas Fúngicas/metabolismo , Interações Hospedeiro-Patógeno , Mucosa Bucal/metabolismo , Mucosa Bucal/microbiologia , Ácido Aspártico Endopeptidases/genética , Candidíase Bucal/patologia , Linhagem Celular , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Hifas , Mucosa Bucal/patologia , Mutação
10.
BMC Complement Altern Med ; 19(1): 303, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703673

RESUMO

BACKGROUND: Candida albicans is an opportunistic pathogen that causes oral candidiasis and denture stomatitis. It has also been reported to infect oral mucositis lesions in patients who suffer from cancer affecting the head and neck and who receive chemotherapy and radiotherapy treatments. This study aimed to investigate the effects of two cinnamon bark fractions, i.e., an essential oil and an aqueous extract enriched in proanthocyanidins (Cinnulin PF®) on growth, biofilm formation, and adherence properties of C. albicans as well as on oral epithelial cells (barrier integrity, inflammatory response). METHODS: A microplate dilution assay was used to determine antifungal and anti-biofilm properties. A fluorescent assay was used to determine C. albicans adherence to oral epithelial cells. Cytotoxicity toward oral epithelial cells was assessed by determination of cell metabolic activity. Tight junction integrity of gingival keratinocytes was assessed by determination of transepithelial electrical resistance. IL-6 and IL-8 secretion by TNFα-stimulated oral epithelial cells was quantified by ELISA. RESULTS: While Cinnulin PF® did not reduce C. albicans growth, the cinnamon bark oil exhibited high antifungal activity with minimum inhibitory concentrations and minimum fungicidal concentrations in the range of 0.039 to 0.078%. The cinnamon oil was also active against a pre-formed C. albicans biofilm. Interestingly, Cinnulin PF® prevented biofilm formation by C. albicans and attenuated its adherence to oral epithelial cells. At their effective concentrations, the cinnamon oil and the Cinnulin PF® displayed no significant cytotoxicity against oral epithelial cells. In an in vitro model, both cinnamon fractions reinforced the integrity of the oral epithelial barrier. Lastly, Cinnulin PF® inhibited the secretion of interleukin-6 and interleukin-8 by oral epithelial cells stimulated with TNF-α. CONCLUSION: By their ability to attenuate growth, biofilm formation and adherence property of C. albicans, to reinforce the epithelial barrier function, and to exert anti-inflammatory properties the two cinnamon fractions (essential oil, Cinnulin PF®) investigated in the present study may be promising agents for treating oral infections involving C. albicans.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase Bucal/microbiologia , Cinnamomum zeylanicum/química , Células Epiteliais/microbiologia , Boca/microbiologia , Óleos Voláteis/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candida albicans/fisiologia , Candidíase Bucal/tratamento farmacológico , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Boca/metabolismo , Casca de Planta/química
11.
mBio ; 10(6)2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719181

RESUMO

Invasive growth in tissues by the human fungal pathogen Candida albicans is promoted by a switch from budding to hyphal morphogenesis that is stimulated by multiple environmental factors that can vary at different sites of infection. To identify genes that promote invasive growth in the oral cavity to cause oropharyngeal candidiasis (OPC), we first identified C. albicans mutants that failed to invade agar medium. Analysis of nine severely defective mutants in a mouse model of OPC revealed that the strongest defects were seen for the rvs161Δ and rvs167Δ mutants, which lack amphiphysin proteins needed for endocytosis. The rvsΔ mutants initially adhered to the tongue but failed to invade efficiently and were lost from the oral cavity. Previous studies indicated that rvsΔ mutants formed filamentous hyphae in the kidney albeit with morphological abnormalities, suggesting that the rvsΔ mutants were influenced by factors that vary at different sites of infection. Consistent with this, increasing concentrations of CO2, an inducer of hyphal growth that is more abundant in internal organs than air, partially rescued the invasive-growth defects of the rvsΔ mutants in vitro Interestingly, preinduction of the rvsΔ mutants to form hyphae prior to introduction into the oral cavity restored their ability to cause OPC, identifying a key role for endocytosis in initiating invasive hyphal growth. These results highlight the influence of distinct environmental factors in promoting invasive hyphal growth in the oral cavity and indicate that blocking endocytosis could have therapeutic value in preventing the initiation of OPC.IMPORTANCE Oropharyngeal candidiasis (OPC) is a common fungal infection that is associated with severe morbidity. Another concern is that patients at risk for developing OPC often take long courses of antifungal drugs, which can lead to the emergence of drug-resistant C. albicans strains. We therefore identified nine mutants with defects in undergoing invasive hyphal growth in the oral cavity, increasing the number of genes known to be involved in OPC by more than 30%. The two strongest mutants, rvs161Δ and rvs167Δ, have defects in endocytosis. The rvsΔ mutants appear to have a specific defect in initiating invasive growth, as preinducing the cells to form hyphae prior to infection restored their ability to cause OPC. These results indicate that blocking endocytosis could have therapeutic value in preventing the initiation of OPC without leading to development of resistance against drugs currently used to treat fungal infections.


Assuntos
Candida albicans/genética , Candida albicans/imunologia , Candidíase Bucal/imunologia , Candidíase Bucal/microbiologia , Proteínas do Citoesqueleto/genética , Endocitose , Interações Hospedeiro-Patógeno , Deleção de Sequência , Animais , Modelos Animais de Doenças , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Hifas/crescimento & desenvolvimento , Camundongos
12.
Clin Exp Dent Res ; 5(5): 580-582, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31687193

RESUMO

Objectives: Neonatal thrush, also called oral candidiasis, is commonly a clinical diagnosis based on white patches on oral mucosal surfaces. Candida albicans is often associated with it. This clinical study aimed to investigate the presence of C. albicans among newborns with or without clinical findings of candidiasis on oral mucosa. Another aim was to investigate how thrush responded to current therapy by acidic liquids such as lingonberry or lemon juice. Material and methods: Swipe samples were collected from 32 healthy, full-term infants younger than 12 months with or without white patches on oral mucosa. Clinical diagnosis of thrush was made by a community nurse based on thick and yellowish white patches. The routine therapy was oral lingonberry or lemon juice or soda water. Disappearing of patches was controlled by a phone call about 2 weeks after the baseline. Both parents and nurses gave background factors by filling a questionnaire. Results: One (3%) infant without clinical signs was diagnosed with Candida parapsilosis, none with C. albicans. Thrush resembling candidiasis was diagnosed clinically in four (12.5%) children. Three out of four parents reported persisting findings after 2 weeks. Only the maternal mastitis and use of antibiotics were significantly associated with thrush (p = .001). C. albicans was not discovered from babies with clinical thrush. Conclusions: Aetiology of the white patches remained unclear. The current way of treating them with acidic liquids is not efficient. Additional studies are needed.


Assuntos
Antifúngicos/uso terapêutico , Candida albicans/efeitos dos fármacos , Candidíase Bucal/tratamento farmacológico , Citrus/química , Doenças do Recém-Nascido/tratamento farmacológico , Vaccinium vitis-Idaea/química , Bebidas , Candidíase Bucal/diagnóstico , Candidíase Bucal/microbiologia , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/microbiologia
13.
J Mycol Med ; 29(4): 310-316, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31630914

RESUMO

OBJECTIVE: Multilocus sequence typing is a powerful method for genotyping of clinical isolates of Candidaalbicans. Cross-contamination between the patients is an important reason for nosocomial infections. Oropharyngeal candidiasis (OPC) caused by C. albicans is an important problem in patients with head and neck cancer, in Cancer Institute of Tehran. Here we studied the endemic genotypes of C. albicans isolates and the relationship between geographic distributions, potential cross-contaminations and the expression of SAP2 gene, an important gene in oral candidiasis, with MLST groups. MATERIAL AND METHODS: A total of 32 clinical strains of C. albicans isolated from head and neck cancer patients with oropharyngeal candidiasis were subjected to MLST analysis and SAP2 gene expression was analyzed by Real-time PCR. RESULTS: We identified 75 polymorphic sites in 7 loci of C. albicans isolates and 30 diploid sequence types which 27 of them were found as new. After eBURST analysis, our results determined that CC 124 was the most prevalent group among all CCs. SAP2 gene showed high expression in almost all OPC patients' isolates, compared to the control. CONCLUSION: We found few genetically-related as well as identical isolates among the 32 Candida strains which indicated low cross-contaminations among the patients. There was no relationship between C. albicans MLST profiles and their geographic distribution, cancer type and SAP2 gene expression. This lack of correlation was possibly due to the small understudy population; hence, finding more relevance requires studies with a higher number of samples.


Assuntos
Ácido Aspártico Endopeptidases/genética , Candida albicans/genética , Candidíase Bucal/epidemiologia , Candidíase Bucal/microbiologia , Proteínas Fúngicas/genética , Genótipo , Neoplasias de Cabeça e Pescoço/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Candida albicans/classificação , DNA Fúngico/genética , Feminino , Expressão Gênica , Técnicas de Genotipagem , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Técnicas de Tipagem Micológica , Filogenia , Adulto Jovem
14.
Appl Microbiol Biotechnol ; 103(21-22): 9037-9055, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31659418

RESUMO

The invasion of Candida albicans is one of the most common fungal infections seen in clinical practice, and serious drug resistance has been reported in recent years. Therefore, new anti-C. albicans drugs must be introduced. In this research, it was demonstrated that cinnamaldehyde (CA) shows strong antimicrobial activity, with 0.26 mg/mL CA being the minimum inhibitory concentration to manage C. albicans. Extraordinarily, we detected that CA accumulated the intracellular reactive oxygen species (ROS) and enhanced the calcium concentration in the cytoplasm and mitochondria through flow cytometry. In addition, we observed that C. albicans cells released Cytochrome c from the mitochondria to the cytoplasm, depolarized the mitochondrial membrane potential, and activated the metacaspase when exposed to 0.065, 0.13, 0.26, and 0.52 mg/mL CA. Furthermore, to confirm that CA introduces the C. albicans apoptosis, we discovered that when the phosphatidylserine was exposed, DNA damage and chromatin condensation occurred, which were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and 4',6-diamidino-2-phenylindole (DAPI) staining. Finally, demonstrations of phenotype investigation, colony-forming unit (CFU) counts, and periodic acid-Schiff (PAS) staining were conducted to prove that CA possessed the ability to treat oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC). From the above, our research indicates that CA is a promising antifungal candidate when applied to C. albicans infections.


Assuntos
Acroleína/análogos & derivados , Antifúngicos/farmacologia , Apoptose/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candidíase Bucal/tratamento farmacológico , Candidíase Vulvovaginal/tratamento farmacológico , Acroleína/farmacologia , Animais , Cálcio/metabolismo , Candidíase Bucal/microbiologia , Candidíase Bucal/prevenção & controle , Candidíase Vulvovaginal/microbiologia , Candidíase Vulvovaginal/prevenção & controle , Citocromos c/metabolismo , Modelos Animais de Doenças , Feminino , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo
15.
Acta Dermatovenerol Croat ; 27(3): 137-141, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31542055

RESUMO

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.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candidíase Bucal/microbiologia , Pênfigo/microbiologia , Adulto , Anfotericina B/farmacologia , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/patologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Econazol/farmacologia , Feminino , Fluconazol/farmacologia , Humanos , Itraconazol/farmacologia , Cetoconazol/farmacologia , Masculino , Pênfigo/tratamento farmacológico , Pênfigo/patologia , Triazóis/farmacologia
16.
Infect Immun ; 87(12)2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31527130

RESUMO

Candida-associated denture stomatitis (DS) is a persistent and chronic oral infection of the denture-bearing palatal mucosa. DS stems from the ability of the fungal opportunistic pathogen Candida albicans to adhere to denture material and invade palatal tissue. Although DS is the most prevalent form of oral candidiasis, there are currently no feasible therapeutic strategies for the prevention of this recurrent condition. We developed a peptide-based antimicrobial bioadhesive formulation specifically designed for oral topical formulation. In this study, we aimed to evaluate the applicability of the novel formulation for the prevention of C. albicans colonization on denture material and development of clinical disease. To that end, using the latest technological advances in dental digital design and three-dimensional (3D) printing, we fabricated an intraoral device for rats with universal fit. The device was successfully installed and used to develop clinical DS. Importantly, by taking a preventative therapeutic approach, we demonstrated the potential clinical utility of the novel formulation as a safe and feasible prophylactic agent against DS.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase Bucal/prevenção & controle , Cimentos Dentários/farmacologia , Estomatite sob Prótese/prevenção & controle , Animais , Antifúngicos/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/microbiologia , Cimentos Dentários/química , Dentaduras/microbiologia , Modelos Animais de Doenças , Masculino , Mucosa Bucal/microbiologia , Ratos , Ratos Sprague-Dawley , Estomatite sob Prótese/tratamento farmacológico , Estomatite sob Prótese/microbiologia
17.
PLoS One ; 14(9): e0223072, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31557235

RESUMO

AIM: To investigate the correlation between the dorsal tongue porphyrin autofluorescence, revealed using VELscope, and Candida saprophytism. MATERIAL AND METHODS: Consecutive patients underwent an autofluorescence examination by the VELscope device to establish the presence or absence of porphyrin fluorescence. A tongue swab was collected for the Candida cultural test. Sensitivity, specificity, accuracy, negative predictive value and positive predictive value were calculated considering the oral swab as the gold standard. The degree of agreement between the two tests was calculated using Cohen's K coefficient. RESULTS: One hundred twenty-six patients were enrolled. Porphyrin fluorescence method showed a sensitivity of 78%, specificity of 76% and an accuracy of 78%. Negative predictive value and positive predictive value were respectively 90% and 59%. The strength of agreement between the two methods resulted to be moderate (k = 0.551). CONCLUSIONS: Off-label use of tongue autofluorescence examination to detect the presence of Candida species is characterized by a loss of porphyrin fluorescence. The high negative predictive value of porphyrin fluorescence loss suggests its use in preliminary selection of Candida carriers, in order to plan preventive and therapeutic strategies.


Assuntos
Candida/isolamento & purificação , Candidíase Bucal/diagnóstico , Imagem Molecular/métodos , Imagem Óptica/métodos , Porfirinas/química , Língua/diagnóstico por imagem , Adulto , Idoso , Biópsia , Candida/metabolismo , Candidíase Bucal/microbiologia , Feminino , Fluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Porfirinas/metabolismo , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Língua/microbiologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-31332066

RESUMO

Oral candidiasis (OC) caused by the fungal pathogen Candida albicans is the most common opportunistic infection in immunocompromised populations. The dramatic increase in resistance to common antifungal agents has emphasized the importance of identifying alternative therapeutic options. Antimicrobial peptides have emerged as promising drug candidates due to their antimicrobial properties; specifically, histatin-5 (Hst-5), a peptide naturally produced and secreted by human salivary glands, has demonstrated potent activity against C. albicans However, as we previously demonstrated vulnerability for Hst-5 to proteolysis by C. albicans proteolytic enzymes at specific amino acid residues, a new variant (K11R-K17R) was designed with amino acid substitutions at the identified cleavage sites. The new resistant peptide demonstrated no cytotoxicity to erythrocytes or human oral keratinocytes. To evaluate the potential of the new peptide for clinical application, we utilized our FDA-approved polymer-based bioadhesive hydrogel as a delivery system and developed a therapeutic formulation specifically designed for oral topical application. The new formulation was demonstrated to be effective against C. albicans strains resistant to the traditional antifungals, and the in vitro therapeutic efficacy was found to be comparable to that of the common topical antifungal agents in clinical use. Importantly, in addition to its antifungal properties, our findings also demonstrated that the new peptide variant induces cell proliferation and rapid cell migration of human oral keratinocytes, indicative of wound healing properties. The findings from this study support the progression of the novel formulation as a therapeutic agent against oral candidiasis, as well as a therapeutic modality for promoting wound healing.


Assuntos
Anti-Infecciosos/farmacologia , Antifúngicos/farmacologia , Hidrogéis/farmacologia , Peptídeos/farmacologia , Cicatrização/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/microbiologia , Linhagem Celular , Histatinas/farmacologia , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/microbiologia
19.
Front Immunol ; 10: 1465, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31316513

RESUMO

Background: Chronic periodontitis (CP), caused by bacteria and fungi, appears in up to 66% of HIV-patients. The impact and association of HIV-treatment (HAART) and Candida itself has not been properly evaluated in the development and progression of CP. The immunopathogenesis is characterized by CD4+ T-cells activation and the balance between the T-helper 1 (Th1) and T-helper 2 (Th2) or a mixed cytokine profile. Currently, the associated causes of an immune response in HIV-patients with CP is controversial. Our aims were the determination of Candida spp. and cytokine profile in oral samples from HIV-positive patients with CP, considering the CD4+ T cells levels and HAART use. Methods: From 500 HIV-positive patients evaluated, 228 patients were enrolled. Patients were separated in groups: (A) n = 53 (≤200 CD4+ T-cells on HAART); (B) n = 57 (≤200 CD4+ T-cells without HAART); (C) n = 50 (>200 CD4+ T-cells without HAART); (D) n = 68 (>200 CD4+ T-cells on HAART). Candida spp. were isolated from the oral biofilm and crevicular fluid in CHROMagar and confirmed by endpoint PCR. Cytokine levels were measured by beads-based immunoassay in saliva by flow cytometry. Results: 147 patients (64.5%) were positive to Candida spp. and 204 strains were isolated; 138 (67.6%) were C. albicans and the remaining C. non-albicans species (C. glabrata>C. tropicalis>C. krusei>C. dubliniensis). In this study, CHROMagar showed good sensitivity (95%) but poor specificity (68%); since of the 152 samples identified as C. albicans, only 131 were confirmed by PCR; from the 10 samples identified as C. glabrata, only six were confirmed. Finally, of the 42 samples detected as C. tropicalis, only five were confirmed. When evaluating Candida spp. presence, group A and D had higher isolation, while group B had the highest species diversity. Whereas, group C had a significant reduction of Candida spp. Despite the presence of Candida and HAART, we found a Th1/Th2 hybrid profile in the saliva of patients with low CD4+ T-cell count (group A). Conclusion: Abundance and diversity of the Candida spp. detected in HIV-patients with CP could be related to HAART and low CD4+ T-cells levels. Also, the immunosuppression might promote a local Th1/Th2 hybrid cytokine profile.


Assuntos
Candida/imunologia , Candidíase Bucal/imunologia , Periodontite Crônica/imunologia , Citocinas/imunologia , Infecções por HIV/imunologia , Células Th1/imunologia , Células Th2/imunologia , Adulto , Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Candida/classificação , Candida/fisiologia , Candidíase Bucal/microbiologia , Periodontite Crônica/microbiologia , Periodontite Crônica/virologia , Citocinas/metabolismo , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Saliva/efeitos dos fármacos , Saliva/imunologia , Saliva/metabolismo , Especificidade da Espécie , Células Th1/microbiologia , Células Th1/virologia , Células Th2/microbiologia , Células Th2/virologia
20.
Oral Dis ; 25(6): 1573-1580, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31177581

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of Streptococcus salivarius K12 as an adjuvant in treating oral candidiasis. METHODS: A total of 56 patients were participated in the randomized, double-blinded, placebo-controlled clinical trial. The S. salivarius K12 or placebo lozenges plus nystatin tablets were given for up to 4 weeks at 1-week interval and then followed up for 1 week thereafter. We collected and analyzed the mycological and clinical data, treatment course, and safety data. RESULTS: At the end of the treatment, significant differences were found in the mycological cure rates between K12 group and control group (90.48% and 55.56%, respectively, p = 0.008). Survival analysis demonstrated no statistical difference in overall cure rates comprehensively considering mycological cure, clinical improvement, and recurrence (p = 0.078), while statistical difference was found in mycological cure (p = 0.013) between the two groups. The median treatment courses of K12 group and control group were 3 weeks and 4 weeks, respectively. No severe events were reported during the study. CONCLUSION: Streptococcus salivarius K12 exhibited potential efficacy and safety as an adjuvant in treating oral candidiasis by enhancing mycological cure and shortening the treatment course of conventional antifungal therapy in this randomized, double-blinded, placebo-controlled clinical trial. Further large-scale clinical studies are desired to accumulate more evidence for its clinical applications.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Candida albicans/efeitos dos fármacos , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/terapia , Nistatina/administração & dosagem , Nistatina/uso terapêutico , Probióticos/administração & dosagem , Administração Oral , Antibacterianos/efeitos adversos , Candidíase Bucal/microbiologia , Método Duplo-Cego , Humanos , Nistatina/efeitos adversos , Probióticos/efeitos adversos , Recidiva , Streptococcus salivarius
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