Infecção do trato urinário por leveduras do gênero Candida ­ revisão de literatura / Urinary tract infection by yeast of the genus Candida - literature review / Infección del tracto urinario causada por levaduras del género Candida - revisión de la literatura

A ocorrência das infecções do trato urinário (ITU) causadas por leveduras do gênero Candida estão aumentando consideravelmente nas últimas décadas, sendo a Candida albicans a mais comumente diagnosticada como causadora deste tipo de infecções. Contudo, outras espécies, como exemplo da Candida tropicalis, estão emergindo como preocupantes causadores da doença. Neste sentido, o objetivo do presente trabalho é revisar os aspectos relacionados com as ITU causadas por leveduras do gênero Candida. Foi realizada uma pesquisa na base de dados PubMed, buscando artigos sobre a epidemiologia, patogenia e tratamento das ITU causadas por leveduras do gênero Candida. As espécies de Candida são os fungos patogênicos oportunistas mais relevantes causadores de infecções nosocomiais e podem causar infecção no trato urinário, tanto inferior (ureteres, bexiga e uretra) quanto superior (rins), principalmente em pacientes imunocomprometidos. Existem alguns fatores predisponentes, como gênero feminino, idade avançada, diabetes mellitus, hospitalização prolongada, imunossupressão, gravidez, hipertensão, neutropenia, cálculos renais, infecções nosocomiais, terapia antibiótica e procedimentos, como a cateterização, que atuam como facilitadores das ITU por Candida spp. A doença pode ocorrer de forma assintomática, porém, pode evoluir para casos mais graves com comprometimento sistêmico em situações de candidemia que pode causar a morte do paciente, principalmente se tratando de indivíduos imunocomprometidos. Sendo assim, devido ao risco existente, a doença não pode ser negligenciada e um diagnóstico preciso e um tratamento adequado devem ser estabelecidos.

The occurrence of urinary tract infections (UTI) caused by yeasts of the genus Candida has increased considerably in recent decades, with Candida albicans being the most commonly diagnosed as causing this type of infections. However, other species, such as Candida tropicalis, are emerging as worrisome causes of the disease. In this sense, the objective of the present paper is to review the aspects related to the UTI caused by yeasts of the genus Candida. A search was carried out in the PubMed database, searching for articles on the epidemiology, pathogenesis and treatment of UTI caused by yeasts of the genus Candida. Candida species are the most relevant opportunistic pathogenic fungi that cause nosocomial infections and can cause both lower (ureters, bladder and urethra) and upper (kidneys) urinary tract infections, especially in immunocompromised patients. There are some predisposing factors, such as female gender, advanced age, diabetes mellitus, prolonged hospitalization, immunosuppression, pregnancy, hypertension, neutropenia, kidney stones, nosocomial infections, antibiotic therapy and procedures, such as catheterization, that act as facilitators of UTI by Candida spp. The disease can occur asymptomatically, however, it can progress to more severe cases with systemic involvement in situations of candidemia that can cause the death of the patient, especially in immunocompromised individuals. Therefore, due to the existing risk, the disease cannot be neglected and an accurate diagnosis and adequate treatment must be established.

La aparición de infecciones del tracto urinario (ITU) causadas por levaduras del género Candida ha aumentado considerablemente en las últimas décadas. Candida albicans es la infección por levaduras más comúnmente diagnosticada. Sin embargo, otras especies, como la Candida tropicalis, están surgiendo como causa preocupante de la enfermedad. En este sentido, el objetivo del presente trabajo es revisar los aspectos relacionados con la ITU causada por levaduras del género Candida. Se realizó una búsqueda en la base de datos PubMed, buscando artículos sobre la epidemiología, la patogénesis y el tratamiento de la ITU causada por levaduras del género Candida. Las especies de Candida son los hongos patógenos oportunistas más relevantes que causan infecciones nosocomiales y pueden provocar infecciones del tracto urinario inferior (uréteres, vejiga y uretra) y superior (riñones), especialmente en pacientes inmunodeprimidos. Existen algunos factores predisponentes, como el sexo femenino, la edad avanzada, la diabetes mellitus, la hospitalización prolongada, la inmunosupresión, el embarazo, la hipertensión, la neutropenia, los cálculos renales, las infecciones nosocomiales, la terapia con antibióticos y los procedimientos como el cateterismo, que actúan como facilitadores de la ITU por Candida spp. La enfermedad puede presentarse de forma asintomática, pero puede evolucionar a casos más graves con afectación sistémica en situaciones de candidemia que pueden causar la muerte del paciente, especialmente en individuos inmunodeprimidos. Por lo tanto, debido al riesgo existente, no se puede descuidar la enfermedad y se debe establecer un diagnóstico preciso y un tratamiento adecuado.

Targeting the Secreted Aspartic Proteinase (SAP-1) Associated with Virulence in C. albicans by C. cassia Bio-compounds: A Computational Approach

Evaluation of the drug ligand interactions between the C. cassia bio-compounds with the SAP-1 in C. albicans to explore the inhibitory medicinal potential of C. cassia bio-compounds by a computational approach is performed in the present investigation. Antimicrobial assay was done using agar well diffusion method with the crude aqueous and ethanolic extracts of the dried barks of C. cassia against C. albicans. 2D & 3D structures of the active bio-compounds of C. cassia were optimized and the 3D structure of SAP-1 was retrieved from the PDB data bank. In-silico inhibitory potential of the selected C. cassia biocompounds against SAP-1 was done by Auto Dock 2.0 and was visualized with Accelrys discovery studio visualizing tool with the assessment of the molecular properties of the ligands against SAP-1 by molinspiration calculations and further assessment for their drug likeliness. In-vitro analysis showed a promising anti-fungal activity of C. cassia extracts against C. albicans. Cinnamoyl E-acetate and Eugenyl acetate seem to possess promising inhibitory effect to target SAP-1 with a least binding energy of –5.33 and -5.21 Kcal/mol with four hydrogen bonds respectively. Molinspiration assessments showed zero violations for all the C. cassia compounds with the TPSA scores of <140 Å towards the best oral bioavailability. The findings of the study emphasize that cinnamaldehyde, cinnamoyal acetate and eugenol from C. cassia seem to possess a promising inhibitory effect against SAP-1 of C. albicans suggesting the medicinal value of the spice against SAP-1

Evaluation of Anti Candida Effect of Melaleuca alternifolia on Heat Cured Acrylic Resin

Objectives: To evaluate the anti-candida properties of tea tree oil as an additive to heat cured acrylic resin. Materials and methods: Total 24 heat cured samples were prepared without the addition of oil (control), and 24 with additives (20% of pure natural tea tree oil). These disks were inoculated with 0.1 mL of Candida albicans standard inoculum and were rinsed with 0.9% NaCl to remove the loosely attached cells from the surface of the discs. Sabouraud’s dextrose agar plate was used for measuring the attached yeast. The control and treated disks have been placed in distilled water for 1 day, 21 days and 42 days and washed daily with wet cotton. Results: CFU the mean colony forming units for control disks were placed in water and cleaned with wet cotton for 1 day, 21 days and 42 days was 1.5000, 5.0000, 1.0000, respectively and CFU for disks with tea tree oil decreased to 0.8750, 1.6250 and 0.3750 after 1 day, 21 days and 42 days. Tea tree oil incorporated specimens were effective in reducing the growth of C. albicans after storage for 42 days in distilled water. Conclusion: There was a significant reduction in the growth of C. albicans after the addition of oil to heat cured acrylic resin which suggests a new oral topical treatment for denture stomatitis.

Cis-2-dodecenoic Acid Mediates Its Synergistic Effect with Triazoles by Interfering with Efflux Pumps in Fluconazole-resistant Candida albicans / 生物医学与环境科学（英文）

OBJECTIVE@#To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid (BDSF) and fluconazole (FLU) or itraconazole (ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in vivo.@*METHODS@#Minimum inhibitory concentrations (MICs) of antibiotics against two azole-resistant C. albicans were measured by the checkerboard technique, E-test, and time-kill assay. In vivo antifungal synergy testing was performed on mice. Analysis of the relative gene expression levels of the strains was conducted by quantitative reverse-transcription polymerase chain reaction (qRT-PCR).@*RESULTS@#BDSF showed highly synergistic effects in combination with FLU or ITRA with a fractional inhibitory concentration index of ⪕ 0.08. BDSF was not cytotoxic to normal human foreskin fibroblast cells at concentrations of up to 300 μg/mL. The qRT-PCR results showed that the combination of BDSF and FLU/ITRA significantly inhibits the expression of the efflux pump genes CDR1 and MDR1 via suppression of the transcription factors TAC1 and MRR1, respectively, when compared with FLU or ITRA alone. No dramatic difference in the mRNA expression levels of ERG1, ERG11, and UPC2 was found, which indicates that the drug combinations do not significantly interfere with UPC2-mediated ergosterol levels. In vivo experiments revealed that combination therapy can be an effective therapeutic approach to treat candidiasis.@*CONCLUSION@#The synergistic effects of BDSF and azoles may be useful as an alternative approach to control azole-resistant Candida infections.

Risk factors and pathogen analysis of candidemia in cancer patients / 中国肿瘤临床

Objects: To clarify the risk factors of candidemia and to assess the clinical differences that may exist between infection with Candida parapsilosis and that with other Candida species in cancer patients. To statistically analyze the clinical characteristics of Candi-da albicans candidemia and C. parapsilosis candidemia and risk factors for their infections. We aimed at a timely intervention through this type of analysis to avoid susceptible factors and improve the prognosis of patients with candidemia. Methods: We retrospectively included 323 patients with candidemia in Affiliated Cancer Hospital of Zhengzhou University between March 2012 and February 2018 and analyzed the clinical characteristics of these patients to establish the risk factors of candidemia. We performed a comparative anal-ysis of the clinical characteristics of C. parapsilosis infections and non-parapsilosis Candida spp. infections and of C. albicans infections and non-albicans Candida spp. infections. In addition, drug sensitivity tests and analyses were performed with the common antifungal drugs used in Candida infections by a micro-broth dilution method. The statistical software SPSS version 22 was used for the analyses. Results: A total of 323 patients were enrolled and analyzed in this study. Of the isolates, 34.37% were C. albicans and 65.63% were non-albicans Candida spp. Multivariate regression analysis showed that the following factors were associated with the occurrence of C. parapsilosis candidemia: parenteral nutrition (P<0.001), neutropenia (P<0.001), history of receiving chemotherapy (P=0.002), and history of previous antifungal use (P<0.001). Parenteral nutrition was found to be an independent risk factor for C. albicans candi-demia (OR=0.183; 95%CI:0.098?0.340; P<0.001). Conclusions: C. parapsilosis was found to be the primary pathogen in cancer patients with candidemia. Total parenteral nutrition in the intensive care unit at diagnosis and abdominal surgery were independent risk factors of candidemia, and parenteral nutrition was an independent risk factor of C. parapsilosis candidemia. At present, C. parapsilosis is sur-passing C. albicans as the main pathogen of candidemia in cancer patients at our hospital. This study emphasizes the need to assess the possible risk factors for candidemia in cancer patients and aims at strengthening and developing a hospital-based control strategy to prevent the spread of candidemia.

Evaluación in vitro de la actividad antimicrobiana de un propóleo chileno sobre muestras clínicas de exudados bucofaríngeos y cepas ATCC / In vitro evaluation of the antimicrobial activity of a Chilean propolis on clinical samples of oropharyngeal exudates

Propolis is a substance manufactured by Apis mellifera and has been widely used in folk medicine due to its high concentration of bioactive compounds. The purpose of the following study was to characterize and evaluate in vitro the antimicrobial properties of propolis on clinical samples and ATCC strains. The chemical characterization of propolis presents a concentration of total polyphenols of 247 ± 9 mg EAG g-1 MS, flavones and flavonols 75± 4 mg EQ g-1 MS, flavanonones and flavanonols 118 ± 11 EP g-1 MS. HPLC-DAD identified apigenin, galangin, phenethyl ester of caffeic acid and pinocembrin, in addition to 16 compounds by HPLC MS/MS. Chilean propolis is a natural antimicrobial, showing effectiveness in strains ATCC Staphylococcus aureus, Candida albicans, Trichophyton rubrum and clinical samples of Staphylococcus aureus unlike Escherichia coli. These results demonstrate the antimicrobial effectiveness of the synergy of compounds present in propolis against different human pathogens.

El propóleos es una substancia fabricada por Apis mellifera y ha sido utilizado ampliamente en la medicina popular debido a su alta concentración de compuestos bioactivos. El propósito del siguiente estudio fue caracterizar y evaluar in vitro las propiedades antimicrobianas del propóleos sobre muestras clínicas y cepas ATCC. La caracterización química de propóleos presenta una concentración de polifenoles totales de 247 ± 9 mg EAG g-1 de MS, flavonas y flavonoles 75 ± 4 mg EQ g-1 de MS, flavanononas y flavanonoles 118 ± 11 EP g-1 de MS. Mediante HPLC-DAD se identificó apigenina, galangina, fenetil éster del ácido cafeico y pinocembrina, además de 16 compuestos mediante HPLC MS/MS. El propóleos chileno es un antimicrobiano natural, observándose efectividad en cepas ATCC Staphylococcus aureus, Candida albicans, Trichophyton rubrum y muestras clínicas de Staphylococcus aureus a diferencia de Escherichia coli. Estos resultados demuestran la efectividad antimicrobiana de la sinergia de compuestos presentes en el propóleos ante diferentes patógenos humanos.

Alternative Oxidase Promotes Biofilm Formation of Candida albicans / 华中科技大学学报（医学）（英德文版）

This study was designed to analyze the effect of the mitochondrial respiratory pathways of Candida albicans (C.albicans) on the biofilm formation.The 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay was used to measure the metabolic activities of biofilms formed by the C.albicans which were cultured in the presence of respiratory pathways inhibitors.The biofilms formed by the wide type (WT),GOA1-deleted (GOA31),GOA1-reconstituted (GOA32),AOX1a-deleted (AOX1) and AOX1b-deleted (AOX2) C.albicans strains were examined by the XTT reduction assay and fluorescence microscopy.The expression of adhesion-related genes BCR1,ALS1,ALS3,ECE1 and HWP1 in the biofilms formed by the above five C.albicans strains was detected by real time polymerase chain reaction.It was found that the metabolic activity of biofilms formed by C.albicans was decreased in the presence of alternative oxidase inhibitor whereas it was increased in the presence of classical mitochondrial respiratory pathway complex Ⅲ or complex Ⅳ inhibitor.AOX1 strain produced scarce biofilms interspersed with few hyphal filaments.Moreover,no significant changes in the expression of BCR1 and ALS3 were observed in the AOX1 strain,but the expression of ALS1 and ECE1 was down-regulated,and that of HWP1 was up-regulated.These results indicate that both AOX1 and AOX2 can promote the biofilm formation.However,AOX1a primarily plays a regulatory role in biofilm formation in the absence of inducers where the promoting effect is mainly achieved by promoting mycelial formation.

Alternative Oxidase Promotes Biofilm Formation of Candida albicans / 华中科技大学学报（医学）（英德文版）

This study was designed to analyze the effect of the mitochondrial respiratory pathways of Candida albicans (C.albicans) on the biofilm formation.The 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay was used to measure the metabolic activities of biofilms formed by the C.albicans which were cultured in the presence of respiratory pathways inhibitors.The biofilms formed by the wide type (WT),GOA1-deleted (GOA31),GOA1-reconstituted (GOA32),AOX1a-deleted (AOX1) and AOX1b-deleted (AOX2) C.albicans strains were examined by the XTT reduction assay and fluorescence microscopy.The expression of adhesion-related genes BCR1,ALS1,ALS3,ECE1 and HWP1 in the biofilms formed by the above five C.albicans strains was detected by real time polymerase chain reaction.It was found that the metabolic activity of biofilms formed by C.albicans was decreased in the presence of alternative oxidase inhibitor whereas it was increased in the presence of classical mitochondrial respiratory pathway complex Ⅲ or complex Ⅳ inhibitor.AOX1 strain produced scarce biofilms interspersed with few hyphal filaments.Moreover,no significant changes in the expression of BCR1 and ALS3 were observed in the AOX1 strain,but the expression of ALS1 and ECE1 was down-regulated,and that of HWP1 was up-regulated.These results indicate that both AOX1 and AOX2 can promote the biofilm formation.However,AOX1a primarily plays a regulatory role in biofilm formation in the absence of inducers where the promoting effect is mainly achieved by promoting mycelial formation.

Protective Effects of cis-2-Dodecenoic Acid in an Experimental Mouse Model of Vaginal Candidiasis / 生物医学与环境科学（英文）

OBJECTIVE@#To evaluate the efficacy of cis-2-dodecenoic acid (BDSF) in the treatment and prevention of vaginal candidiasis in vivo.@*METHODS@#The activities of different concentrations of BDSF against the virulence factors of Candida albicans (C. albicans) were determined in vitro. An experimental mouse model of Candida vaginitis was treated with 250 μmol/L BDSF. Treatment efficiency was evaluated in accordance with vaginal fungal burden and inflammation symptoms.@*RESULTS@#In vitro experiments indicated that BDSF attenuated the adhesion and damage of C. albicans to epithelial cells by decreasing phospholipase secretion and blocking filament formation. Treatment with 30 μmol/L BDSF reduced the adhesion and damage of C. albicans to epithelial cells by 36.9% and 42.3%, respectively. Treatment with 200 μmol/L BDSF completely inhibited phospholipase activity. In vivo mouse experiments demonstrated that BDSF could effectively eliminate vaginal infection and relieve inflammatory symptoms. Four days of treatment with 250 μmol/L BDSF reduced vaginal fungal loads by 6-fold and depressed inflammation. Moreover, BDSF treatment decreased the expression levels of the inflammatory chemokine-associated genes MCP-1 and IGFBP3 by 2.5- and 2-fold, respectively.@*CONCLUSION@#BDSF is a novel alternative drug that can efficiently control vaginal candidiasis by inhibiting the virulence factors of C. albicans.

Study of the antifungal potential of (r)-(+)-citronellal and its association with therapeutic agents used in the treatment of vulvovaginal candidiasis / Estudo do potencial antifúngico do (r)-(+)-citronelal e sua associação com agentes terapêuticos utilizados no tratamento da candidíase vulvovaginal

Vulvovaginal candidiasis (VVC) is a common fungal infection that affects healthy women of all ages. At least 75% of women will develop one or more infections once during their lifetime, with 6 to 9% of those individuals developing recurrent infections. In view of this context, this study sought to evaluate the antifungal potential of the isolated (R)-(+)-citronellal [(R)-(+)-CT] and associated to therapeutic agents of clinical importance. The enantiomer was solubilized in tween 80 and dimethylsulfoxide (DMSO). Posteriorly diluted in sterile distilled water up to the concentration of 2048µg/mL. The minimum inhibitory concentration (MIC) of the product was determined by microdilution in RPMI-1640 obtaining dilutions of 1024-4µg/mL. The minimum fungicidal concentration (MFC) was determined by the Sabouraud dextrose agar (SDA) depletion technique from aliquots of 1µL of the MIC, MIC × 2 and MIC × 4. The MIC and the MFC values of (R)-(+)-CT for 90% of the C. albicans strains were 16 and 32µg/mL respectively. In the susceptibility test, C. albicans presented a high resistance to fluconazole and to itraconazole, 12 (92.30%) of the strains. However, for ketoconazole and miconazole the resistance was of 4 (30.76%) and 3 (23.07%) of the strains respectively. In the combination testing of the (R)-(+)-CT with ketoconazole and miconazole, the resistance was completely reverted. For fluconazole and itraconazole, the resistance was reverted in 9 (75%) and 7 (58.33%) of the strains respectively. The (R)-(+)-CT presented fungicide activity with MFC of MIC × 2. When in combination with ketoconazole, fluconazole, itraconazole and miconazole increased the inhibition zones of these antifungal drugs, reducing the resistance against C. albicans.

Candidíase vulvovaginal (CVV) é uma infecção fúngica comum que afeta mulheres saudáveis de todas as idades. Pelo menos 75% das mulheres irão desenvolver uma ou mais infecções uma vez durante a vida, com 6 a 9% dos indivíduos desenvolvendo infecções recorrentes. Diante deste contexto, buscou-se avaliar neste estudo o potencial antifúngico do (R)-(+)-citronelal [(R)-(+)-CT] isolado e associado a agentes terapêuticos de importância clínica. O enantiômero foi solubilizado em tween 80 e dimetilsulfóxido (DMSO). Posteriormente diluiu-se em água destilada estéril até a concentração de 2048µg/mL. A concentração inibitória mínima (CIM) do produto foi determinada por microdiluição em meio RPMI-1640 obtendo diluições de 4-1024µg/mL. A concentração fungicida mínima (CFM) foi determinada pela técnica de esgotamento em agar Sabouraud dextrose (ASD) a partir de alíquotas de 1mL da CIM, CIM × 2 e CIM × 4. A CIM e a CFM do (R)-(+)-CT para 90% das cepas de C. albicans foram 16 e 32µg/mL respectivamente. No ensaio de suscetibilidade, C. albicans apresentou alta resistência ao fluconazol e ao itraconazol, 12 (92.30%) das cepas. No em tanto, para o cetoconazol e o miconazol a resistência foi de 4 (30.76%) e 3 (23.07%) das cepas respectivamente. No ensaio de combinação do (R)-(+)-CT com cetoconazol e miconazol, a resistência foi completamente revertida. Para o fluconazol e o itraconazol, a resistências foi revertida em 9 (75%) e 7 (58.33%) das cepas respectivamente. O (R)-(+)-CT apresentou atividade fungicida com CFM igual à CIM × 2. Quando em combinação com cetoconazol, fluconazol, itraconazol e miconazol ampliou as zonas de inibição desses antifúngicos, diminuindo a resistência contra C. albicans.

Rapid identification of inactivated C.albicans by surface-enhanced Raman spectroscopy / 药学实践杂志

Objective To develop a rapid method for the identification of inactivated C.albicans by surface-enhanced Raman spectroscopy (SERS).Methods Live C.albicans cultures were exposed to heating, formaldehyde and fungicidal drug (amphotericin B).The corresponding SERS spectra were acquired for the investigation and comparison.Results The spectra acquired with three different inactivation methods exhibited similar features of dead C.albicans, which showed significant difference from the spectra of the live culture.Conclusion This SERS method can identify the inactivated C.albicans rapidly.Hopefully it will provide a convenient tool for quick identification of other inactivated pathogenic microorganisms.

Effect of catestatin on inhibiting C.albicans biofilm formation by down-regulating the expression of HWP1 / 中国感染与化疗杂志

Objective To investigate whether catestatin (bovine chromogranin A 344-364) can inhibit the biofilm formation of Candida albicans and examine its relationship with the expression of adhesion gene HWP1.Methods Clinical strains and standard strain ATCC 10231 of C.albicans were studied.XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] method was used to assess the ability of C.albicans biofilm formation.Antifungal activity against planktonic Candida ceils was evaluated in terms of minimum inhibitory concentrations (MICs) according to the description in CLSI-M27-A3.XTT assay and colony count were used to assess the effect of catestatin on inhibiting C.albicans biofilm formation.The lowest concentration showing 50 ％ inhibition on biofilm formation (BIC50) was decided by calculating the metabolic activity.The adhesion of C.albicans reduced by catestatin was visualized under an inverted microscope and quantified by colony count.The expression of HWP1 was analyzed by RT-PCR.One-way analysis of variance (ANOVA) and Dunnett's T3 test were used to compare the results.Results Clinical strains and standard strain ATCC 10231 of C.albicans showed strong ability in forming biofilm.Catestatin exhibited MICs ranging from 40 μmol/L to 80 μmol/L against planktonic C.albicans cells,and BIC50 of 80-160 μmol/L in inhibiting C.albicans biofilm formation.Catestatin reduced the adhesion of C.albicans.The colony forming unit (CFU) was 27 822.22-±-2 472.74 in blank control group,while the CFU was 5 355.55± 1 264.03,11 377.78±2 232.58,17 488.89±1 136.27,22 377.78±3 521.99,and 26 044.44±1 329.57 in the presence of 160,80,40,20,and 10 μmol/L catestatin,respectively (F=147.018,P=0.001).The difference between control group and 160,80,and 40 μmol/L catestatin was statistically significant (P＜0.05).RT-PCR found the expression of HWP1 in the presence of 160 μmol/L catestatin was about 12.24％ of that in blank control group.Conclusions Catestatin can effectively prevent C.albicans biofilm formation.This effect may be related to the down-regulated expression of adhesion gene HWP1 by catestatin,which results in reduced adhesion of C.albicans.Promising clinical prospect is expected for this finding.

Actividad in vitro de extractos etanólicos de propóleos del bajo cauca antioqueño sobre dos hongos filamentosos y uno levaduriforme

El propóleos es una resina colectada por las abejas Apis mellifera de especies botánicas, próximas a los apiarios. Este material resinoso es ampliamente reconocido por sus propiedades antimicrobianas. El objetivo de este trabajo fue evaluar la actividad antifúngica in vitro de los extractos etanólicos de propóleos (EEP), obtenidos a partir de muestras provenientes de apiarios experimentales de investigación, ubicados en la región del Bajo Cauca antioqueño, sobre dos hongos filamentosos, Botryodiplodia theobromae y Fusarium oxysporum y un hongo levaduriforme, Candida albicans El propóleos fue recolectado por los métodos de malla y de raspado, durante diferentes periodos del año. Mediante la técnica de macrodilución en caldo, se evaluaron seis dosis de EEP, en un rango de156 a 5000µgmL-1 y se determinó la concentración que inhibió el 80 y el 50% del crecimiento del hongo. Los resultados indican que el método de recolección del propóleos presentó diferencias significativas con respecto al crecimiento de C albicans y no para B theobromae y F oxysporum Las CMI80 estuvieron entre 1211 a 4050µgmL-1, 1567 a 5016µgmL-1 y 1529 a 3568µgmL-1 para B theobromae, F oxysporum y C albicans, respectivamente. En conclusión, los extractos evaluados exhibieron un actividad inhibitoria del crecimiento moderada, en comparación con el control y el hongo levaduriforme, C albicans presentó la mayor sensibilidad frente a los EEP analizados. Adicionalmente, el método de recolección del propóleos solo presentó diferencias significativas respecto a la concentración mínima inhibitoria, encontrada para C albicans.

Propolis is a resin collected by the Apis mellifera bees from botanical species surrounding the apiaries. This resinous material is widely renowned by its antimicrobial properties. The aim of this research was to evaluate the in vitro activity of ethanolic extracts from propolis (EEP), obtained from experimental research apiaries located in the Bajo Cauca antioqueño region, against two filamentous fungi, Botryodiplodia theobromae and Fusarium oxysporum, and a yeast, Candida albicans. Propolis were collected in different periods of the year, by methods of scraping and mesh. Using the macrodilution technique, six doses of EEP ranging from 156 to 5000µgmL-1 were evaluated and minimal inhibitory concentration 80 and inhibitory concentration 50 were determined. Results indicated that the harvest method showed a significant effect on C albicans growth, but not for B theobromae and F oxysporum. The MICs80 observed were between 1211 to 4050µgmL-1, 1567 to 5016µgmL-1 and 1529 to 3568µgmL-1 for B theobromae, F oxysporum and C albicans, respectively. In conclusion, the extracts tested showed a moderate inhibitory growth activity, in comparison with the control; the yeast, C albicans, showed the highestsensibility to the EEP evaluated. Additionally, the collection methods only showed significant differences with respect to minimal inhibitory concentration found for C albicans.

Therapeutic effect of ellagic acid on Candida albicans infect mice models and its antifungal activity in vitro / 中国药理学通报

Aim To investigate the inhibitory effect of ellagic acid( EA) on fungal strains both in vitro and in vivo. Methods The minimal inhibitory concentration ( MIC ) was determined by the NCCLS ( M27-A2 ) standard method in vitro. The therapeutic action was studied using a Candida albicans infect mice model, the survival rate and the content of SOD, MDA in ser-um were measured, and the pathological changes of liver were observed under light microscope after HE staining. Results EA was active against three Candida strains, with MICs between 25. 0 and 75. 0 mg·L-1 . The most sensitive Candida species was C. albicans ( MIC=25. 0 mg·L-1 ) . It was inactive against Can-dida glabrata. An in vivo test demonstrated that intrap-eritoneal injection of EA(40 and 80 mg·kg-1 ) signif-icantly enhanced the pathological changes of liver, im-proved the symptom, increased the weight and the SOD activity, and decreased the MDA activity in a mice in-fection model of C. albicans. Conclusion Ellagic acid has the potential to be developed as a natural antifungal agent.

Antifungal effects of synthetic human β-defensin 3-C15 peptide

OBJECTIVES: The purpose of this ex vivo study was to compare the antifungal activity of a synthetic peptide consisting of 15 amino acids at the C-terminus of human β-defensin 3 (HBD3-C15) with calcium hydroxide (CH) and Nystatin (Nys) against Candida albicans (C. albicans) biofilm. MATERIALS AND METHODS: C. albicans were grown on cover glass bottom dishes or human dentin disks for 48 hr, and then treated with HBD3-C15 (0, 12.5, 25, 50, 100, 150, 200, and 300 µg/mL), CH (100 µg/mL), and Nys (20 µg/mL) for 7 days at 37℃. On cover glass, live and dead cells in the biomass were measured by the FilmTracer Biofilm viability assay, and observed by confocal laser scanning microscopy (CLSM). On dentin, normal, diminished and ruptured cells were observed by field-emission scanning electron microscopy (FE-SEM). The results were subjected to a two-tailed t-test, a one way analysis variance and a post hoc test at a significance level of p = 0.05. RESULTS: C. albicans survival on dentin was inhibited by HBD3-C15 in a dose-dependent manner. There were fewer aggregations of C. albicans in the groups of Nys and HBD3-C15 (≥ 100 µg/mL). CLSM showed C. albicans survival was reduced by HBD3-C15 in a dose dependent manner. Nys and HBD3-C15 (≥ 100 µg/mL) showed significant fungicidal activity compared to CH group (p < 0.05). CONCLUSIONS: Synthetic HBD3-C15 peptide (≥ 100 µg/mL) and Nys exhibited significantly higher antifungal activity than CH against C. albicans by inhibiting cell survival and biofilm.

Multilocus sequence typing and genetic diversity ofCandida albicans in patients with vulvovaginal candidiasis / 中国感染与化疗杂志

Objective To investigate the molecular epidemiology of 114C. albicans strains isolated from the vaginal discharge of female patients treated in three obstetrics and gynecology hospitals in Shanghai by analyzing the relationship between the main genotypes and resistance proifle, and the relationship between genetic diversity and cluster ofC. albicans.Methods A total of 114 strains ofC. albicans were collected from the Obstetrics & Gynecology Hospital of Fudan University, Shanghai First Maternity and Infant Hospital Corporation and the International Peace Maternity & Child Health Hospital of China welfare institute. Phylogenetic analysis of strains were carried out by eBURST.C. albicans strains were also analyzed by multilocus sequence typing (MLST). The susceptibility of theC. albicans strains was tested by ATB FUNGUS 3.Results A total of 47 diploid strain types (DSTs) were identiifed from the 114 strains, 30 of which were known types. DST 79 and DST 435 were the main types. Of the 114C. albicans strains, 96.5% were susceptible to lfucytosine, 100% to amphotericin B, 85.1% to lfuconazole, 55.2% to itraconazole and 84.3% to voriconazole.Conclusions The pathogenicC. albicans strains isolated from different obstetrics and gynecology hospitals in Shanghai were originated from multiple clones, the main type of which was DST 79 and DST 435 with certain degree of antifungal resistance. MLST typing suggests that genetic diversity is present in theC. albicans strains isolated in Shanghai area. The clustering analysis ofC. albicans strains is consistent with its genotypes.

CHEMICAL CHARACTERIZATION AND EVALUATION OF ANTIBACTERIAL, ANTIFUNGAL, ANTIMYCOBACTERIAL, AND CYTOTOXIC ACTIVITIES OF Talinum paniculatum / Caracterização química e avaliação das atividades antibacteriana, antifúngica, antimicobacteriana e citotóxica de Talinum paniculatum

SUMMARY In this study, the bioactivity of Talinum paniculatum was evaluated, a plant widely used in folk medicine. The extract from the T. paniculatum leaves (LE) was obtained by percolation with ethanol-water and then subjecting it to liquid-liquid partitions, yielding hexane (HX), ethyl acetate (EtOAc), butanol (BuOH), and aqueous (Aq) fractions. Screening for antimicrobial activity of the LE and its fractions was evaluated in vitro through broth microdilution method, against thirteen pathogenic and non-pathogenic microorganisms, and the antimycobacterial activity was performed through agar diffusion assay. The cytotoxic concentrations (CC90) for LE, HX, and EtOAc were obtained on BHK-21 cells by using MTT reduction assay. The LE showed activity against Serratia marcescens and Staphylococcus aureus, with Minimum Inhibitory Concentration (MIC) values of 250 and 500 µg/mL, respectively. Furthermore, HX demonstrated outstanding activity against Micrococcus luteus and Candida albicans with a MIC of 31.2 µg/mL in both cases. The MIC for EtOAc also was 31.2 µg/mL against Escherichia coli. Conversely, BuOH and Aq were inactive against all tested microorganisms and LE proved inactive against Mycobacterium tuberculosisand Mycobacterium bovisas well. Campesterol, stigmasterol, and sitosterol were the proposed structures as main compounds present in the EF and HX/EtOAc fractions, evidenced by mass spectrometry. Therefore, LE, HX, and EtOAc from T. paniculatumshowed potential as possible sources of antimicrobial compounds, mainly HX, for presenting low toxicity on BHK-21 cells with excellent Selectivity Index (SI = CC90/MIC) of 17.72 against C. albicans.

RESUMO Neste estudo foi avaliada a bioatividade de Talinum paniculatum, planta amplamente utilizada na medicina popular. O extrato das folhas (EF) de T. paniculatum foi obtido por percolação com etanol-água e, em seguida, submetido à partição líquido-líquido, obtendo-se as frações hexânica (HX), acetato-etílica (AcOEt), butanólica (BuOH) e aquosa (Aq). A triagem para a atividade antimicrobiana do EF e de suas frações foram avaliadas in vitro através do método de microdiluição em caldo contra treze micro-organismos patogênicos e não-patogênicos e, a atividade antimicobacteriana, foi avaliada através do teste de difusão em ágar. As concentrações citotóxicas (CC90) do EF e das frações HX e AcOEt foram obtidas sobre células da linhagem BHK-21 através do ensaio de redução do MTT. O EF mostrou atividade contra Serratia marcescens e Staphylococcus aureus, com valores de concentração inibitória mínima (CIM) de 250 e 500 µg/mL, respectivamente. Além disso, HX demonstrou excelente atividade contra Micrococcus luteus e Candida albicans com uma CIM de 31,2 µg/mL, em ambos os casos. Contra Escherichia coli, a CIM para AcOEt foi também de 31,2 µg/mL. Por outro lado, as frações BuOH e Aq foram inativas contra todos os micro-organismos testados, assim como o EF contra Mycobacterium tuberculosis e Mycobacterium bovis. Campesterol, estigmasterol e sitosterol foram as estruturas propostas como principais compostos presentes no EF e nas frações HX e AcOEt, evidenciadas através de espectrometria de massas. Portanto, o extrato da folha e as frações HX e AcOEt provenientes de T. paniculatum apresentaram potencial como possíveis fontes de compostos antimicrobianos, HX principalmente, por ter apresentado uma baixa toxicidade sobre células BHK-21 com um bom índice de seletividade (IS = CC90/MIC) de 17,72 contra C. albicans.

BAY 41-2272 activates host defence against local and disseminated Candida albicans infections

In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation. .

Effects of Globeflower Residue Fermentation Extraction on Anti-Candida albicans in vivo and in vitro / 世界科学技术-中医药现代化

This study was aimed to observe the antibacterial activity and bactericidal action ofC.albicans in vitro, and the effects of curing monilial vaginitis mouse by extraction of globeflower residue fermentation (EGRF) in vivo.In vitrostudy, test tube method as well as plate method were used to determine the minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) ofC.albicansrespectively.In vivo, mouse were devided into normal controlled group,C. albicans vaginitis model group (Model), Model + EGRF (40, 80, 160 mg?kg-1) group, and fluconazole group (20 mg?kg-1). All drugs were vaginal delivery once a day with continuous administration for seven days. Then vulva inflammation, negative rate of vaginal discharge, microbial load of vaginal lavage and the pathological changes of vaginal mucosa were observed. After the treatment of EGRF, the MIC and MBC of Candida albicans were 0.31 mg?mL-1 and 1.25 mg?mL-1, respectively, while the potency unit ratios between EGRF and fluconazole of MIC and MBC were 2 to 1 and 1 to 1, respectively. In comparison with Model, vulva inflammation of Model + EGRF gourp and fluconazole group was improved, whileC. albicanscount in vaginal secretions of these two groups were decreased, the overcast rate ofC. albicansof vaginal douche was increased, and pathological changes of vaginal mucosa were also improved in the two groups, which were in dose-dependent manners. And high dose Model + EGRF group was close to fluconazole group. In conclusion, EGRF had obvious inhibitory effect onC. albicans in vitro. It also had a better therapeutic effect onC. albicans vaginitis mouse.

Evaluation and comparison of anti-Candida effect of heat cure polymethylmethacrylate resin enforced with silver nanoparticles and conventional heat cure resins: An in vitro study.

Recent years have been dominated by research in nano science. Dentistry is no exception and there is increased research on nanoparticles in dentistry. Complete dentures increase the carriage of Candida in healthy patients, and the proliferation of C. albicans can be associated with denture-induced stomatitis. Purpose: To evaluate the anti-Candida effect of heat cure denture base resins reinforced with Ag° in the ratio of 4:1, 3:1, 2:1 (Groups B, C, and D, respectively) to the weight of denture base resins. Materials and Methods: Ag° were synthesized by chemical reduction method, incorporated into the polymer powder according to the ratio for each group, subjected to polymerization and microbial assay was calculated for the reference C. albicans strains by agar diffusion method for the incubation period of 24 h. Results: Group D showed multifold decrease in the colony-forming units. Conclusion: The antimicrobial effect of silver could be used vividly in the denture base for immunocompromised and geriatric patients.