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1.
Med Mycol J ; 61(3): 33-48, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32863327

RESUMO

Kawasaki disease (KD) is an inflammatory disease that was identified by Professor Tomisaku Kawasaki in 1961. Candida albicans-derived substances (CADS) such as the hot water extract of C. albicans and Candida water-soluble fractions (CAWS) induce coronary vasculitis similar to KD in mice. An increasing proportion of deep-seated candidiasis cases are caused by non-albicans Candida and are often resistant to antifungal drugs. We herein investigated whether the mannoprotein fractions (MN fractions) of clinically isolated Candida species induce vasculitis in mice. We prepared MN fractions from 26 strains of Candida species by conventional hot water extraction and compared vasculitis in DBA/2 mice. The results obtained revealed that the induction of vasculitis and resulting heart failure were significantly dependent on the species; namely, death rates on day 200 were as follows: Candida krusei (100%), Candida albicans (84%), Candida dubliniensis (47%), Candida parapsilosis (44%), Candida glabrata (32%), Candida guilliermondii (20%), and Candida tropicalis (20%). Even for C. albicans, some strains did not induce vasculitis. The present results suggest that MN-induced vasculitis is strongly dependent on the species and strains of Candida, and also that the MN fractions of some non-albicans Candida induce similar toxicity to those of C. albicans.


Assuntos
Candida albicans/química , Candida albicans/patogenicidade , Candidíase , Vasos Coronários/microbiologia , Proteínas Fúngicas/efeitos adversos , Vasculite/microbiologia , Animais , Candida albicans/classificação , Fracionamento Celular , Proteínas Fúngicas/isolamento & purificação , Camundongos Endogâmicos DBA , Especificidade da Espécie
2.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(7): 1049-1055, 2020 Jul 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895165

RESUMO

OBJECTIVE: To investigate the characteristics of growth and metabolism and the in vivo toxicity of Candida auris under different conditions. METHODS: We observed the growth of Candida auris and Candida albicans under routine culture conditions and in different pH and salt concentrations, and compared their activities of sugar fermentation using microbiochemical reaction tubes. Four-week-old nude mice were randomized into Candida auris infection group (n=5), Candida albicans infection group (n=5) and control group (n=5) for intragastric administration of 0.3 mL suspension the two Candida species (5×109 cfu/mL) or 0.3 mL normal saline. Samples of the liver, kidney, intestine, feces and blood were taken for analysis of the in vivo distribution and toxicity of Candida albicans by fungal culture and histopathological examination. RESULTS: Candida auris exhibited logarithmic growth at 8-24 h after inoculation and showed stable growth after 24 h. Candida auris showed optimal growth within the pH value range of 5-7 with a growth pattern identical to that of Candida albicans. Candida auris grew better than Candida albicans in media containing 5% and 10% NaCl, and could ferment glucose, sucrose, trehalose and sorbitol. Candida auris could be isolated from the feces, blood, liver and kidney of infected nude mice, and the liver had the highest fungal load (5.7 log10 cfu/g). Candida auris could cause pathological changes in the liver and intestine of the mice, but with a lesser severity as compared with Candida albicans. CONCLUSIONS: Candida auris exhibits optimal growth in mildly acidic or neutral conditions with a high salt tolerance, and can potentially penetrate the intestinal barrier into blood and lead to tissue injuries in hosts with immunosuppression.


Assuntos
Candida , Candidíase , Animais , Antifúngicos , Candida albicans , Fígado , Camundongos , Camundongos Nus
3.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(4): 431-437, 2020 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-32865364

RESUMO

Oral cancer is the most common malignant tumor in the head and neck, and is one of the world's top ten malignancies. Microbial infection is an important risk factor of oral cancer. Candida albicans is the most popular opportunistic fungal pathogen. Epidemiological studies have shown that Candida albicans is closely tied to oral malignancy. Animal experimentation have also proven that infection of Candida albicans can promote the development of oral epithelial carcinogenesis. The current studies have revealed several mechanisms involved in this process, including destroying the epithelial barrier, producing carcinogenic substances (nitrosamines, acetaldehyde), inducing chronic inflammation, activating immune response, etc. However, current researches on mechanisms are still inadequate, and some hypotheses remain controversial. Here, we review the findings related to Candida albicans' effect on the malignant transformation of oral mucosa, hoping to provide reference for deep research and controlling oral cancer clinically.


Assuntos
Doenças da Boca , Neoplasias Bucais , Animais , Candida albicans , Carcinogênese , Mucosa Bucal
4.
BMC Infect Dis ; 20(1): 599, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32795259

RESUMO

BACKGROUND: Fungal bloodstream infections (FBI) among intensive care unit (ICU) patients are increasing. Our objective was to characterize the fungal pathogens that cause bloodstream infections and determine the epidemiology and risk factors for patient mortality among ICU patients in Meizhou, China. METHODS: Eighty-one ICU patients with FBI during their stays were included in the study conducted from January 2008 to December 2017. Blood cultures were performed and the antimicrobial susceptibility profiles of the resulting isolates were determined. Logistic multiple regression and ROC curve analysis were used to assess the risk factors for mortality among the cases. RESULTS: The prevalence of FBI in ICU patients was 0.38% (81/21,098) with a mortality rate of 36% (29/81). Ninety-eight strains of bloodstream-infecting fungi, mainly Candida spp., were identified from these patients. Candida albicans was most common (43%). Two strains of C. parapsilosis were no-sensitive to caspofungin, C. glabrata were less than 80% sensitive to azole drugs. Logistic multiple regression showed that age, serum albumin, APACHE II score, three or more underlying diseases, and length of stay in ICU were independent risk factors for mortality in FBI. ROC curve analysis showed that APACHE II scores > 19 and serum albumin ≤25 g/L were the best predictors of mortality. CONCLUSION: Candida spp. predominated with high mortality rates among cases of FBI in ICU. Thus, clinical staff should enhance overall patient monitoring and concurrently monitor fungal susceptibility to reduce mortality rates.


Assuntos
Micoses/patologia , APACHE , Idoso , Antifúngicos/uso terapêutico , Área Sob a Curva , Azóis/uso terapêutico , Candida albicans/isolamento & purificação , Candida parapsilosis/isolamento & purificação , China/epidemiologia , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/epidemiologia , Micoses/mortalidade , Prevalência , Curva ROC , Fatores de Risco
5.
Zhongguo Zhong Yao Za Zhi ; 45(13): 3211-3219, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32726031

RESUMO

To observe the efficacy of cinnamaldehyde on dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) with Can-dida albicans(Ca) colonization and its effect on dectin-1/TLRs/NF-κB signaling pathway in mice. C57 BL/6 mice were randomly divided into normal group, DSS group, DSS+Ca group, cinnamaldehyde group and mesalazine group. Mice in DSS+Ca group were given Ca(1×10~8 CFU per mouse) through intragastrical administration for 4 consecutive days and then distilled water with 3.0% DSS for 7 consecutive days. In cinnamaldehyde group and mesalazine group, in addition to the induction method of the DSS+Ca group, mice were given 75 mg·kg~(-1) cinnamaldehyde and 200 mg·kg~(-1) mesalazine accompanied with 3.0% DSS for 7 consecutive days, respectively. Mice in normal group and DSS group were correspondingly administered with distilled water. The general conditions of the mice were observed daily, the diseased activity index(DAI) score was calculated, and fungal loads of feces were detected by plate method. The mice were sacrificed on day 12, colon length was measured, colon mucosa damage index(CMDI) score was calculated, and histopathological analysis was carried out by HE staining. Anti-saccharomces cerevisiae antibody(ASCA) and ß-1,3-glucan in serum, and TNF-α, IL-1ß, IL-6, IL-8, IL-10 in serum and colon tissue were detected by ELISA. The contents of ß-1,3-glucan and macrophage infiltration in colon tissues were examined by immunofluorescence staining. The protein expressions of dectin-1, TLR2, TLR4 and NF-κB were detected by Western blot and immunohistochemistry staining. The results showed that cinnamaldehyde could significantly improve the general conditions of UC mice with Ca colonization, decrease DAI and histopathological scores, reduce intestinal mucosal congestion, erosion and colon shortening, decrease Ca load in mouse feces and tissues, down-regulate the contents of ASCA and ß-1,3-glucan in serum, reduce the contents of TNF-α, IL-1ß, IL-6, IL-8 and increase IL-10 in serum and colon tissues, inhibit macrophages infiltration and down-regulate the protein expression of dectin-1, TLR2, TLR4 and NF-κB in colon tissue. These results suggested that cinnamaldehyde had a therapeutic effect on UC mice with Ca colonization, which might be related to the inhibition of Ca proliferation, the regulation of dectin-1/TLRs/NF-κB signaling pathways and the coordination of the balance between pro-inflammatory and anti-inflammatory factors.


Assuntos
Colite Ulcerativa , Acroleína/análogos & derivados , Animais , Candida albicans , Colo , Sulfato de Dextrana , Modelos Animais de Doenças , Lectinas Tipo C , Camundongos , NF-kappa B , Transdução de Sinais
6.
PLoS One ; 15(7): e0236095, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726358

RESUMO

The Fungitell assay (FA) and the Wako ß-glucan test (GT) are employed to measure the serum/plasma 1,3-ß-D-glucan (BDG), a well-known invasive fungal disease biomarker. Data to convincingly and/or sufficiently support the GT as a valuable alternative to the FA are yet limited. In this study, we evaluated the FA and the GT to diagnose invasive aspergillosis (IA), invasive candidiasis (IC), and Pneumocystis jirovecii pneumonia (PJP). The FA and GT performances were compared in sera of patients with IA (n = 40), IC (n = 78), and PJP (n = 17) with respect to sera of control patients (n = 187). Using the manufacturer's cutoff values of 80 pg/mL and 11 pg/mL, the sensitivity and specificity for IA diagnosis were 92.5% and 99.5% for the FA and 60.0% and 99.5% for the GT, respectively; for IC diagnosis were 100.0% and 97.3% for the FA and 91.0% and 99.5% for the GT, respectively; for PJP diagnosis were 100.0% and 97.3% for the FA and 88.2% and 99.5% for the GT, respectively. When an optimized cutoff value of 7.0 pg/mL for the GT was used, the sensitivity and specificity were 80.0% and 97.3% for IA diagnosis, 98.7% and 97.3% for IC diagnosis, and 94.1% and 97.3% for PJP diagnosis, respectively. At the 7.0-pg/mL GT cutoff, the agreement between the assays remained and/or became excellent for IA (95.1%), IC (97.3%), and PJP (96.5%), respectively. In conclusion, we show that the GT performed as well as the FA only with a lowered cutoff value for positivity. Further studies are expected to establish the equivalence of the two BDG assays.


Assuntos
Aspergilose/diagnóstico , Candidíase Invasiva/diagnóstico , Testes Diagnósticos de Rotina/métodos , Pneumonia por Pneumocystis/diagnóstico , beta-Glucanas/análise , Adulto , Idoso , Aspergilose/sangue , Aspergilose/microbiologia , Aspergillus/imunologia , Aspergillus/isolamento & purificação , Candida albicans/imunologia , Candida albicans/isolamento & purificação , Candidíase Invasiva/sangue , Candidíase Invasiva/microbiologia , Testes Diagnósticos de Rotina/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/imunologia , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/sangue , Pneumonia por Pneumocystis/microbiologia , Curva ROC
7.
PLoS Genet ; 16(7): e1008908, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32639995

RESUMO

The human fungal pathogen Candida albicans is constantly exposed to environmental challenges impacting the cell wall. Signaling pathways coordinate stress adaptation and are essential for commensalism and virulence. The transcription factors Sko1, Cas5, and Rlm1 control the response to cell wall stress caused by the antifungal drug caspofungin. Here, we expand the Sko1 and Rlm1 transcriptional circuit and demonstrate that Rlm1 activates Sko1 cell wall stress signaling. Caspofungin-induced transcription of SKO1 and several Sko1-dependent cell wall integrity genes are attenuated in an rlm1Δ/Δ mutant strain when compared to the treated wild-type strain but not in a cas5Δ/Δ mutant strain. Genome-wide chromatin immunoprecipitation (ChIP-seq) results revealed numerous Sko1 and Rlm1 directly bound target genes in the presence of caspofungin that were undetected in previous gene expression studies. Notable targets include genes involved in cell wall integrity, osmolarity, and cellular aggregation, as well as several uncharacterized genes. Interestingly, we found that Rlm1 does not bind to the upstream intergenic region of SKO1 in the presence of caspofungin, indicating that Rlm1 indirectly controls caspofungin-induced SKO1 transcription. In addition, we discovered that caspofungin-induced SKO1 transcription occurs through self-activation. Based on our ChIP-seq data, we also discovered an Rlm1 consensus motif unique to C. albicans. For Sko1, we found a consensus motif similar to the known Sko1 motif for Saccharomyces cerevisiae. Growth assays showed that SKO1 overexpression suppressed caspofungin hypersensitivity in an rlm1Δ/Δ mutant strain. In addition, overexpression of the glycerol phosphatase, RHR2, suppressed caspofungin hypersensitivity specifically in a sko1Δ/Δ mutant strain. Our findings link the Sko1 and Rlm1 signaling pathways, identify new biological roles for Sko1 and Rlm1, and highlight the complex dynamics underlying cell wall signaling.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Candida albicans/efeitos dos fármacos , Caspofungina/farmacologia , Proteínas de Domínio MADS/genética , Proteínas Repressoras/genética , Proteínas de Saccharomyces cerevisiae/genética , Antifúngicos/farmacologia , Candida albicans/genética , Candida albicans/patogenicidade , Parede Celular/efeitos dos fármacos , Parede Celular/genética , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Humanos , Fosforilação/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/genética
8.
J Contemp Dent Pract ; 21(5): 509-514, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32690832

RESUMO

AIM: The purpose of this study was to compare the antifungal activity of three concentrations of a hydroethanolic extract of the Musa × paradisiaca peel against Candida albicans strain ATCC 10231. MATERIALS AND METHODS: The agar diffusion method was used, and the culture medium used was Sabouraud agar. Petri dishes were prepared with concentrations of 10, 30, and 50% of hydroethanolic extract of the M. × paradisiaca peel; nystatin was used as a positive control, and 96% ethanol was used as a negative control. After 24 hours of incubation, each plate was examined, and the diameters (mm) of the growth inhibition halos were measured around each well using a digital vernier caliper. RESULTS: The results showed that the antifungal activity of the extract varied, depending on the concentration, as shown using analysis of variance (ANOVA; p < 0.05). When comparing the different concentrations, it was found by Duncan test that the greatest activity was obtained at 50%. CONCLUSION: It was concluded that the hydroethanolic extract of M. × paradisiaca at 50% exerted a greater antifungal effect on the strain of C. albicans than did the extract at lower concentrations. CLINICAL SIGNIFICANCE: By knowing the antimicrobial effect of M. × paradisiaca, this substance can be effectively used in products aimed to cure candidiasis infection.


Assuntos
Candida albicans , Musa , Antifúngicos , Testes de Sensibilidade Microbiana , Nistatina , Peru
9.
PLoS One ; 15(7): e0235746, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32678853

RESUMO

Azole resistant fungal infections remain a health problem for the immune compromised. Current therapies are limited due to rises in new resistance mechanisms. Therefore, it is important to identify new drug targets for drug discovery and novel therapeutics. Arv1 (are1 are2 required for viability 1) function is highly conserved between multiple pathogenic fungal species. Candida albicans (C. albicans) cells lacking CaArv1 are azole hypersusceptible and lack virulence. Saccharomyces cerevisiae (S. cerevisiae) Scarv1 cells are also azole hypersusceptible, a phenotype reversed by expression of CaArv1, indicating conservation in the molecular mechanism for azole susceptibility. To define the relationship between Arv1 function and azole susceptibility, we undertook a structure/function analysis of ScArv1. We identified several conserved amino acids within the ScArv1 homology domain (ScAhd) required for maintaining normal azole susceptibility. Erg11 lanosterol 14-α-demethylase is the rate-limiting enzyme in sterol biosynthesis and is the direct target of azole antifungals, so we used our ScArv1 mutants in order to explore the relationship between ScArv1 and ScErg11. Specific ScArv1 mutants ectopically expressed from a low copy plasmid were unable to restore normal azole susceptibility to Scarv1 cells and had reduced Erg11 protein levels. Erg11 protein stability depended on its ability to form a heterodimeric complex with Arv1. Complex formation was required for maintaining normal azole susceptibility. Scarv1 cells expressing orthologous CaArv1 mutants also had reduced CaErg11 levels, were unable to form a CaArv1-CaErg11 complex, and were azole hypersusceptible. Scarv1 cells expressing CaArv1 mutants unable to interact with CaErg11 could not sustain proper levels of the azole resistant CaErg11Y132F F145L protein. Caarv1/Caarv1 cells expressing CaArv1 mutants unable to interact with CaErg11 were found to lack virulence using a disseminated candidiasis mouse model. Expressing CaErg11Y132F F145L did not reverse the lack of virulence. We hypothesize that the role of Arv1 in Erg11-dependent azole resistance is to stabilize Erg11 protein level. Arv1 inhibition may represent an avenue for treating azole resistance.


Assuntos
Candida albicans/patogenicidade , Candidíase/microbiologia , Sistema Enzimático do Citocromo P-450/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Esterol 14-Desmetilase/metabolismo , Virulência , Sequência de Aminoácidos , Animais , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Sistema Enzimático do Citocromo P-450/genética , Farmacorresistência Fúngica , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Homologia de Sequência , Esterol 14-Desmetilase/genética
10.
Autoimmun Rev ; 19(9): 102621, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32693029

RESUMO

Candida albicans is a commensal fungus with a potential pathogenicity and celiac disease is an autoimmune condition. Both share multiple pathophysiological junctions, including serological markers against cell-wall proteins of Candida, anti-gliadin antibodies are positive in both entities, gluten and a candidal virulence factor share sequence similarity and the autoantigen of celiac disease, the tissue transglutaminase, is pivotal in Candida albicans commensalism and hostile behavior and its covalently cross linked products are stable and resistant to breakdown in the two entities. Those autoimmune/infectious cross roads are the basis for the hypothesis that Candida albicans is an additional environmental factor for celiac disease autoimmunogenesis.


Assuntos
Candida albicans/patogenicidade , Doença Celíaca/microbiologia , Anticorpos/imunologia , Autoantígenos/química , Autoantígenos/imunologia , Autoimunidade , Candida albicans/imunologia , Doença Celíaca/imunologia , Gliadina/imunologia , Humanos , Transglutaminases/química , Transglutaminases/imunologia , Fatores de Virulência/química , Fatores de Virulência/imunologia
11.
J Indian Soc Pedod Prev Dent ; 38(2): 152-157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32611861

RESUMO

Background: Early childhood caries (ECC) is an aggressive, destructive form of dental caries that affects the children younger than 6 years of age. Candida is known to increase the adherence of Streptococcus mutans to the oral biofilm and produce acids that cause tooth demineralization. Aim of the Study: To evaluate the efficacy of six commercially available children's toothpaste on clinical isolates of Candida albicans obtained from ECC patients. Materials and Methods: The study population comprised 60 children aged 3-6 years having ECC. Samples were divided into six groups comprising ten children in each group. Samples were collected using sterile cotton swabs, inoculated on Sabouraud dextrose agar, and incubated at 37°C for 24 h. Species identification was done by germ tube test and growth on corn meal agar. After the confirmed growth of C. albicans, the six commercially available children's toothpaste namely Organic Children's Coconut Oil Toothpaste®, Aloe Dent Children's Toothpaste®, Patanjali Dant Kanti Junior Toothpaste®, Colgate Kids Toothpaste®, Pediflor Kids Toothpaste®, and Crest Pro-Health Stages Kids Toothpaste® and distilled water as control group were subjected for antifungal activity of C. albicans. Agar plates were incubated at 37°C for 48 h, and the diameter of the zones of inhibition was measured and recorded. Data were tabulated and statistical analysis was done using Statistical Package for the Social Science (16.0) version. Results: Pediflor kids toothpaste® showed maximum antifungal activity and Aloe Dent children's toothpaste® showed minimum antifungal activity. Conclusion: All brands of children's toothpaste show antifungal activity against Candida albicans.


Assuntos
Candida albicans , Cárie Dentária , Antifúngicos , Criança , Pré-Escolar , Humanos , Streptococcus mutans , Cremes Dentais
12.
Int J Nanomedicine ; 15: 4351-4362, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606682

RESUMO

Purpose: The present study synthesized silver nanoparticles (AgNPs) using the aqueous extract of a traditional medicinal product consisting of an oleoresin (a combination of macromolecules of carbohydrates and proteins) exuded from the rhizome of the plant Ferula foetida (asafoetida gum) and evaluated its biological properties. Materials and Methods: The silver nanoparticles synthesized using asafoetida gum (As-AgNPs) were characterized using UV/Vis spectroscopy, fourier infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) with energy dispersive X-ray analysis (EDX), X-ray diffraction (XRD) and transmission electron microscopy (TEM) and EADX. The cytotoxicity and antimicrobial activity As-AgNPs were evaluated against MCF-7 cell lines and selected microbial pathogens, respectively. Results: The synthesized silver nanoparticles were crystalline in nature with a spherical shape. The average particle size was 5.6-8.6 nm. The cytotoxicity of the synthesized As-AgNPs was evaluated against MCF-7 cell lines, and the As-AgNPs were found to be effective in inhibiting the multiplication of cancer cells. The As-AgNPs exhibited significant antimicrobial activity towards E. coli, K. pneumoniae and C. albicans. The MIC of the synthesized As-AgNPs was 7.80 µg/mL for E. coli ATCC 25922, Salmonella sp. WS50- and S. typhi; 15.60 µg/mL for S. typhimurium and S. aureus WS10, and 31.20 µg/mL for K. pneumoniae and S. aureus ATCC 43300-MRSA. In addition, MIC values of 15.60 µg/mL for C. albicans ATCC8436 and 31.20 µg/mL for C. krusei ATCC6258 were obtained. Conclusion: As asafoetida is a good traditional medicine, its involvement in the synthesis of AgNPs led the silver nanoparticles to exhibit good cytotoxic and antimicrobial effects.


Assuntos
Anti-Infecciosos/farmacologia , Ferula/química , Nanopartículas Metálicas/química , Gomas Vegetais/química , Prata/farmacologia , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Células MCF-7 , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Extratos Vegetais/química , Staphylococcus aureus/efeitos dos fármacos , Difração de Raios X
13.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 40(7): 1049-1055, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32701244

RESUMO

OBJECTIVE: To investigate the characteristics of growth and metabolism and the in vivo toxicity of Candida auris under different conditions. METHODS: We observed the growth of Candida auris and Candida albicans under routine culture conditions and in different pH and salt concentrations, and compared their activities of sugar fermentation using microbiochemical reaction tubes. Four-week-old nude mice were randomized into Candida auris infection group (n=5), Candida albicans infection group (n=5) and control group (n=5) for intragastric administration of 0.3 mL suspension the two Candida species (5×109 cfu/mL) or 0.3 mL normal saline. Samples of the liver, kidney, intestine, feces and blood were taken for analysis of the in vivo distribution and toxicity of Candida albicans by fungal culture and histopathological examination. RESULTS: Candida auris exhibited logarithmic growth at 8-24 h after inoculation and showed stable growth after 24 h. Candida auris showed optimal growth within the pH value range of 5-7 with a growth pattern identical to that of Candida albicans. Candida auris grew better than Candida albicans in media containing 5% and 10% NaCl, and could ferment glucose, sucrose, trehalose and sorbitol. Candida auris could be isolated from the feces, blood, liver and kidney of infected nude mice, and the liver had the highest fungal load (5.7 log10 cfu/g). Candida auris could cause pathological changes in the liver and intestine of the mice, but with a lesser severity as compared with Candida albicans. CONCLUSIONS: Candida auris exhibits optimal growth in mildly acidic or neutral conditions with a high salt tolerance, and can potentially penetrate the intestinal barrier into blood and lead to tissue injuries in hosts with immunosuppression.


Assuntos
Candida , Candidíase , Animais , Candida/crescimento & desenvolvimento , Candida/isolamento & purificação , Candida albicans/crescimento & desenvolvimento , Candidíase/microbiologia , Meios de Cultura , Camundongos , Camundongos Nus , Distribuição Aleatória
14.
BMC Infect Dis ; 20(1): 506, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32660641

RESUMO

BACKGROUND: We evaluated the epidemiology, clinical characteristics, microbiology, outcomes, and risk factors for mortality of candidemia in adult surgical patients in Shenyang from 2012 to 2018. METHODS: We designed a retrospective observational study of adult patients with candidemia in a teaching hospital including three hospital campuses. Data regarding clinical and demographic characteristics were collected from the patient's medical records. RESULTS: Of the 236 cases of candidemia, 172 (72.9%) were identified in surgical patients, including 146 (84.9%) general surgeries, 11 (6.4%) urologic surgeries, 6 (3.5%) thoracic surgeries, and others. Higher proportions of solid tumors, total parenteral nutrition, the presence of a urinary catheter, and the presence of a gastric tube were observed in surgical patients with candidemia versus non-surgical ones, whereas the percentages of hematological malignancy, diabetes mellitus, and renal replacement therapy were relatively lower in surgical patients. Renal failure, leukopenia, and thrombocytopenia were less common laboratory findings in surgical patients with candidemia than compared to non-surgical ones. Among surgical patients with candidemia, Candida parapsilosis was the predominant species (43%), followed by C. albicans (33.7%), C. glabrata (11%), C. tropicalis (8.1%), and others (4.1%). Overall susceptibility, susceptible dose dependent or intermediate susceptibility, and resistance to fluconazole were detected in 73.3, 19.8, and 3.5% Candida isolates from surgical patients, respectively, but no resistance to amphotericin B was observed. Overall, the 30-day mortality in surgical patients was 19.2%. At multivariable analysis, independent risk factors for death in surgical patients with candidemia were ICU stay, thrombocytopenia, and C. albicans infection. CONCLUSIONS: Surgical patients account for the majority of candidemia cases. Among patients with recent surgery, risk factors for species distribution, antifungal sensitivity patterns of Candida isolates causing candidemia, and independent risk factors for mortality should be evaluated and considered for a better outcome in the antifungal treatment.


Assuntos
Candida albicans/isolamento & purificação , Candida parapsilosis/isolamento & purificação , Candidemia/epidemiologia , Candidemia/mortalidade , Complicações Pós-Operatórias/microbiologia , Adulto , Idoso , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Candidemia/tratamento farmacológico , Candidemia/microbiologia , China/epidemiologia , Feminino , Fluconazol/uso terapêutico , Hospitais de Ensino , Humanos , Incidência , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
15.
PLoS Genet ; 16(6): e1008881, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32525871

RESUMO

Iron is an essential nutrient required as a cofactor for many biological processes. As a fungal commensal-pathogen of humans, Candida albicans encounters a range of bioavailable iron levels in the human host and maintains homeostasis with a conserved regulatory circuit. How C. albicans senses and responds to iron availability is unknown. In model yeasts, regulation of the iron homeostasis circuit requires monothiol glutaredoxins (Grxs), but their functions beyond the regulatory circuit are unclear. Here, we show Grx3 is required for virulence and growth on low iron for C. albicans. To explore the global roles of Grx3, we applied a proteomic approach and performed in vivo cross-linked tandem affinity purification coupled with mass spectrometry. We identified a large number of Grx3 interacting proteins that function in diverse biological processes. This included Fra1 and Bol2/Fra2, which function with Grxs in intracellular iron trafficking in other organisms. Grx3 interacts with and regulates the activity of Sfu1 and Hap43, components of the C. albicans iron regulatory circuit. Unlike the regulatory circuit, which determines expression or repression of target genes in response to iron availability, Grx3 amplifies levels of gene expression or repression. Consistent with the proteomic data, the grx3 mutant is sensitive to heat shock, oxidative, nitrosative, and genotoxic stresses, and shows growth dependence on histidine, leucine, and tryptophan. We suggest Grx3 is a conserved global regulator of iron-dependent processes occurring within the cell.


Assuntos
Candida albicans/fisiologia , Candidíase Invasiva/microbiologia , Proteínas Fúngicas/metabolismo , Glutarredoxinas/metabolismo , Ferro/metabolismo , Animais , Candida albicans/patogenicidade , Modelos Animais de Doenças , Proteínas Fúngicas/genética , Proteínas Fúngicas/isolamento & purificação , Fatores de Transcrição GATA/metabolismo , Regulação Fúngica da Expressão Gênica , Glutarredoxinas/genética , Glutarredoxinas/isolamento & purificação , Homeostase , Humanos , Hifas , Masculino , Camundongos , Mutação , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/genética , Proteômica , Virulência/genética
16.
Int J Nanomedicine ; 15: 3681-3693, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547022

RESUMO

Background: Fungal infections are becoming more prevalent and threatening because of the continuous emergence of azole-resistant fungal infections. The present study was aimed to assess the activity of free Methylglyoxal (MG) or MG-conjugated chitosan nanoparticles (MGCN) against fluconazole-resistant Candida albicans. Materials and Methods: A novel formulation of MGCN was prepared and characterized to determine their size, shape and polydispersity index. Moreover, the efficacy of fluconazole or MG or MGCN was determined against intracellular C. albicans in macrophages and the systematic candidiasis in a murine model. The safety of MG or MGCN was tested in mice by analyzing the levels of hepatic and renal toxicity parameters. Results: Candida albicans did not respond to fluconazole, even at the highest dose of 20 mg/kg, whereas MG and MGCN effectively eliminated C. albicans from the macrophages and infected mice. Mice in the group treated with MGCN at a dose of 10 mg/kg exhibited a 90% survival rate and showed the lowest fungal load in the kidney, whereas the mice treated with free MG at the same dose exhibited 50% survival rate. Moreover, the administration of MG or MGCN did not induce any liver and kidney toxicity in the treated mice. Conclusion: The findings of the present work suggest that MGCN may be proved a promising therapeutic formulation to treat azole-resistant C. albicans infections.


Assuntos
Candidíase/tratamento farmacológico , Quitosana/química , Farmacorresistência Fúngica , Fluconazol/uso terapêutico , Nanopartículas/química , Aldeído Pirúvico/uso terapêutico , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candidíase/microbiologia , Modelos Animais de Doenças , Farmacorresistência Fúngica/efeitos dos fármacos , Feminino , Fluconazol/farmacologia , Hifas/efeitos dos fármacos , Hifas/crescimento & desenvolvimento , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Nanopartículas/ultraestrutura , Tamanho da Partícula , Aldeído Pirúvico/farmacologia
17.
PLoS One ; 15(6): e0234239, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32525884

RESUMO

Hummingbirds are essential pollinators in many ecosystems, making their conservation critical. As is the case with many species, hummingbirds are now facing a variety of challenges resulting from anthropogenic changes. As populations shift and species interactions change, disease is likely to pose a significant threat. There is a basic understanding of which pathogens currently affect a variety of hummingbird species, however there is a paucity of information about their immune systems capacity to kill pathogens and what specific factors may affect immunity. The objective of this study was to gain a basic understanding of the effect of age, sex, and molt on the constitutive innate immunity of hummingbirds. An in vitro assay was used to assess the microbiocidal capacity of the whole blood of Anna's Hummingbirds (Calypte anna) against three different microbes: Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Candida albicans (C. albicans). The effect of age, sex and molt on anti-microbial capacity varied based on the microbe type. After-hatch-year birds tended to have better anti-microbial capacity compared to hatch-year birds. Male birds had higher anti-microbial activity than female birds, although this was not observed against C. albicans. Molting birds had a weaker antimicrobial activity against E. coli and S. aureus than birds that were not molting. These results represent an important first step towards defining the parameters of constitutive innate immunity of Anna's Hummingbirds as well as providing important knowledge about factors that should be considered when evaluating the health of wild populations.


Assuntos
Aves/sangue , Plasma/metabolismo , Animais , Aves/crescimento & desenvolvimento , Candida albicans/fisiologia , Escherichia coli/fisiologia , Feminino , Masculino , Viabilidade Microbiana , Muda , Caracteres Sexuais , Staphylococcus aureus/fisiologia
18.
Braz Oral Res ; 34: e050, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578760

RESUMO

Candida infection is an important cause of morbidity and mortality in immunocompromised patients. The increase in its incidence has been associated with resistance to antimicrobial therapy and biofilm formation. The aim of this study was to evaluate the efficacy of tea tree oil (TTO) and its main component - terpinen-4-ol - against resistant Candida albicans strains (genotypes A and B) identified by molecular typing and against C. albicans ATCC 90028 and SC 5314 reference strains in planktonic and biofilm cultures. The minimum inhibitory concentration, minimum fungicidal concentration, and rate of biofilm development were used to evaluate antifungal activity. Results were obtained from analysis of the biofilm using the cell proliferation assay 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and confocal laser scanning microscopy (CLSM). Terpinen-4-ol and TTO inhibited C. albicans growth. CLSM confirmed that 17.92 mg/mL of TTO and 8.86 mg/mL of terpinen-4-ol applied for 60 s (rinse simulation) interfered with biofilm formation. Hence, this in vitro study revealed that natural substances such as TTO and terpinen-4-ol present promising results for the treatment of oral candidiasis.


Assuntos
Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Óleo de Melaleuca/farmacologia , Terpenos/farmacologia , Resinas Acrílicas , Análise de Variância , Antifúngicos/farmacologia , Biofilmes/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Bases de Dentadura/microbiologia , Testes de Sensibilidade Microbiana , Microscopia Confocal , Valores de Referência , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Óleo de Melaleuca/química , Terpenos/química
19.
Nature ; 582(7810): 109-114, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32494068

RESUMO

Advances in genetics and sequencing have identified a plethora of disease-associated and disease-causing genetic alterations. To determine causality between genetics and disease, accurate models for molecular dissection are required; however, the rapid expansion of transcriptional populations identified through single-cell analyses presents a major challenge for accurate comparisons between mutant and wild-type cells. Here we generate mouse models of human severe congenital neutropenia (SCN) using patient-derived mutations in the GFI1 transcription factor. To determine the effects of SCN mutations, we generated single-cell references for granulopoietic genomic states with linked epitopes1, aligned mutant cells to their wild-type equivalents and identified differentially expressed genes and epigenetic loci. We find that GFI1-target genes are altered sequentially, as cells go through successive states of differentiation. These insights facilitated the genetic rescue of granulocytic specification but not post-commitment defects in innate immune effector function, and underscore the importance of evaluating the effects of mutations and therapy within each relevant cell state.


Assuntos
Modelos Animais de Doenças , Células Precursoras de Granulócitos/patologia , Mutação , Neutropenia/genética , Neutropenia/patologia , Neutrófilos/patologia , Animais , Candida albicans/imunologia , Candida albicans/patogenicidade , Linhagem da Célula , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Imunidade Inata , Masculino , Camundongos , Camundongos Transgênicos , Neutropenia/congênito , Neutropenia/imunologia , Neutrófilos/imunologia , Fatores de Transcrição/genética
20.
Arch Microbiol ; 202(7): 1977-1984, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32476046

RESUMO

Biofilm-mediated multidrug resistance has turned into major challenge for the treatment of C. albicans infections. In the present study, actinomycetes (SS5) isolated from marine crustacean were investigated for their ability to inhibit C. albicans biofilm formation. Cultural, morphological and 16S rRNA analysis revealed that the isolated strain was Streptomyces diastaticus. Ethyl acetate bioactive fractions (6 µg mL-1) from SS5 showed potent antibiofilm activity against C. albicans. Light microscopic and CLSM analysis further substantiated the antibiofilm activity of the bioactive fraction against C. albicans. The bioactive fraction was subjected to FTIR and GC-MS for characterization. From GC-MS analysis, the presence of 31 compounds were revealed, among which the alkanes are predominantly present. Hence, further investigation for the potential of these bioactive compounds against C. albicans biofilm will help in the identification of promising candidate for the prevention of biofilm-mediated infection.


Assuntos
Antibiose/fisiologia , Biofilmes , Candida albicans/fisiologia , Streptomyces/fisiologia , Antifúngicos , Testes de Sensibilidade Microbiana , RNA Ribossômico 16S/genética , Streptomyces/classificação , Streptomyces/isolamento & purificação
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