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1.
Methods Mol Biol ; 2477: 419-437, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35524130

RESUMO

The ability of living organisms to survive changing environmental conditions is dependent on the implementation of gene expression programs underlying adaptation and fitness. Transcriptional networks can be exceptionally complex: a single transcription factor (TF) may regulate hundreds of genes, and multiple TFs may regulate a single gene-depending on the environmental conditions. Moreover, the same TF may act as an activator or repressor in distinct conditions. In turn, the activity of regulators themselves may be dependent on other TFs, as well as posttranscriptional and posttranslational regulation. These traits greatly contribute to the intricate networks governing gene expression programs.In this chapter, a step-by-step guide of how to use PathoYeastract, one of several interconnecting databases within the YEASTRACT+ portal, to predict gene and genomic regulation in Candida spp. is provided. PathoYeastract contains a set of analysis tools to study regulatory associations in human pathogenic yeasts, enabling: (1) the prediction and ranking of TFs that contribute to the regulation of individual genes; (2) the prediction of the genes regulated by a given TF; and (3) the prediction and ranking of TFs that regulate a genome-wide transcriptional response. These capabilities are illustrated, respectively, with the analysis of: (1) the TF network controlling the C. glabrata QDR2 gene; (2) the regulon controlled by the C. glabrata TF Rpn4; and (3) the regulatory network controlling the C. glabrata transcriptome-wide changes induced upon exposure to the antifungal drug fluconazole. The newest potentialities of this information system are explored, including cross-species network comparison. The results are discussed considering the performed queries and integrated with the current knowledge on the biological data for each case-study.


Assuntos
Candida , Genômica , Candida/genética , Candida/metabolismo , Redes Reguladoras de Genes , Genômica/métodos , Humanos , Regulon , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
2.
J Enzyme Inhib Med Chem ; 37(1): 876-894, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35296203

RESUMO

With increasing number of immunocompromised patients as well as drug resistance in fungi, the risk of fatal fungal infections in humans increases as well. The action of echinocandins is based on the inhibition of ß-(1,3)-d-glucan synthesis that builds the fungal cell wall. Caspofungin, micafungin, anidulafungin and rezafungin are semi-synthetic cyclic lipopeptides. Their specific chemical structure possess a potential to obtain novel derivatives with better pharmacological properties resulting in more effective treatment, especially in infections caused by Candida and Aspergillus species. In this review we summarise information about echinocandins with closer look on their chemical structure, mechanism of action, drug resistance and usage in clinical practice. We also introduce actual trends in modification of this antifungals as well as new methods of their administration, and additional use in viral and bacterial infections.


Assuntos
Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Candida/efeitos dos fármacos , Desenho de Fármacos , Equinocandinas/farmacologia , Antifúngicos/química , Aspergillus/metabolismo , Candida/metabolismo , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Equinocandinas/química , Glucanos/antagonistas & inibidores , Glucanos/metabolismo , Testes de Sensibilidade Microbiana , Estrutura Molecular
3.
Bioresour Technol ; 352: 127087, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35358675

RESUMO

A hybrid machine learning (ML) aided experimental approach was proposed in this study to evaluate the growth kinetics of Candida antarctica for lipase production. Different ML models were trained and optimized to predict the growth curves at various substrate concentrations. Results on comparison demonstrate the superior performance of the Gradient boosting regression (GBR) model in growth curves prediction. GBR-based growth kinetics was found to be matching well with the results of the conventional experimental approach while significantly reducing the experimental effort, time, and resources by âˆ¼ 50%. Further, the activity and enzyme kinetics of lipase produced in this study was investigated on hydrolysis of p-nitrophenyl butyrate resulting in a maximum lipase activity of 24.07 U at 44 h. The robustness and significance of developed kinetic models were ensured through detailed statistical analysis. The application of the proposed hybrid approach can be extended to any other microbial process.


Assuntos
Candida , Lipase , Basidiomycota , Candida/metabolismo , Enzimas Imobilizadas/metabolismo , Proteínas Fúngicas , Cinética , Lipase/metabolismo , Aprendizado de Máquina
4.
Int J Mol Sci ; 23(4)2022 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-35216181

RESUMO

Resistance to antifungal therapy of Candida albicans and non-albicans Candida strains, frequently associated with oral candidosis, is on the rise. In this context, host-defense peptides have emerged as new promising candidates to overcome antifungal resistance. Thus, the aim of this study was to assess the effectiveness against Candida species of different Catestatin-derived peptides, as well as the combined effect with serum albumin. Among Catestatin-derived peptides, the most active against sensitive and resistant strains of C. albicans, C. tropicalis and C. glabrata was the D-isomer of Cateslytin (D-bCtl) whereas the efficiency of the L-isomer (L-bCtl) significantly decreases against C. glabrata strains. Images obtained by transmission electron microscopy clearly demonstrated fungal membrane lysis and the leakage of the intracellular material induced by the L-bCtl and D-bCtl peptides. The possible synergistic effect of albumin on Catestatin-derived peptides activity was investigated too. Our finding showed that bovine serum albumin (BSA) when combined with the L- isomer of Catestatin (L-bCts) had a synergistic effect against Candida albicans especially at low concentrations of BSA; however, no synergistic effect was detected when BSA interacted with L-bCtl, suggesting the importance of the C-terminal end of L-bCts (GPGLQL) for the interaction with BSA. In this context in vitro D-bCtl, as well as the combination of BSA with L-bCts are potential candidates for the development of new antifungal drugs for the treatment of oral candidosis due to Candida and non-Candida albicans, without detrimental side effects.


Assuntos
Candidíase Bucal/tratamento farmacológico , Cromogranina A/farmacologia , Fragmentos de Peptídeos/farmacologia , Peptídeos/farmacologia , Animais , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/metabolismo , Candidíase Bucal/metabolismo , Bovinos , Farmacorresistência Fúngica/efeitos dos fármacos , Humanos , Soroalbumina Bovina/metabolismo
5.
Chem Biodivers ; 19(3): e202100757, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35092349

RESUMO

Candida species are responsible for causing invasive candidiasis with high mortality rate and their resistance to available antifungal drugs is a major clinical challenge. Biotransformation process of the labdane diterpene ent-labd-8(17)-en-15,18-dioic acid (1) carried out with Cunninghamella elegans afforded five new derivatives (compounds 2-6). Unusual regioselective hydroxylation of the methyl group at the C-20 position of labdane-type diterpene was achieved and all compounds were subjected to cytotoxicity and antifungal evaluations. Compound 1 and its derivatives were not cytotoxic to normal (MCF-10A) and tumor (MCF-7) cell lines. Compounds 2 and 3 exhibited fungistatic activity against all tested Candida strains at lower concentrations than fluconazole. Both compounds also showed the strongest fungicidal activity against C. albicans, which is the most prevalent fungal agent involved in candidemia.


Assuntos
Candida , Diterpenos , Antifúngicos/farmacologia , Biotransformação , Candida/metabolismo , Cunninghamella , Diterpenos/metabolismo , Diterpenos/farmacologia , Fluconazol , Testes de Sensibilidade Microbiana
6.
Microbiol Spectr ; 10(1): e0087321, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35019680

RESUMO

The limited number of available effective agents necessitates the development of new antifungals. We report that jervine, a jerveratrum-type steroidal alkaloid isolated from Veratrum californicum, has antifungal activity. Phenotypic comparisons of cell wall mutants, K1 killer toxin susceptibility testing, and quantification of cell wall components revealed that ß-1,6-glucan biosynthesis was significantly inhibited by jervine. Temperature-sensitive mutants defective in essential genes involved in ß-1,6-glucan biosynthesis, including BIG1, KEG1, KRE5, KRE9, and ROT1, were hypersensitive to jervine. In contrast, point mutations in KRE6 or its paralog SKN1 produced jervine resistance, suggesting that jervine targets Kre6 and Skn1. Jervine exhibited broad-spectrum antifungal activity and was effective against human-pathogenic fungi, including Candida parapsilosis and Candida krusei. It was also effective against phytopathogenic fungi, including Botrytis cinerea and Puccinia recondita. Jervine exerted a synergistic effect with fluconazole. Therefore, jervine, a jerveratrum-type steroidal alkaloid used in pharmaceutical products, represents a new class of antifungals active against mycoses and plant-pathogenic fungi. IMPORTANCE Non-Candida albicans Candida species (NCAC) are on the rise as a cause of mycosis. Many antifungal drugs are less effective against NCAC, limiting the available therapeutic agents. Here, we report that jervine, a jerveratrum-type steroidal alkaloid, is effective against NCAC and phytopathogenic fungi. Jervine acts on Kre6 and Skn1, which are involved in ß-1,6-glucan biosynthesis. The skeleton of jerveratrum-type steroidal alkaloids has been well studied, and more recently, their anticancer properties have been investigated. Therefore, jerveratrum-type alkaloids could potentially be applied as treatments for fungal infections and cancer.


Assuntos
Alcaloides/farmacologia , Antifúngicos/farmacologia , Parede Celular/metabolismo , Fungos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Veratrum/química , beta-Glucanas/metabolismo , Alcaloides/isolamento & purificação , Antifúngicos/isolamento & purificação , Candida/efeitos dos fármacos , Candida/genética , Candida/metabolismo , Parede Celular/efeitos dos fármacos , Fungos/genética , Fungos/metabolismo , Humanos , Micoses/microbiologia , Extratos Vegetais/isolamento & purificação
7.
Biotechnol Lett ; 44(1): 89-99, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34738223

RESUMO

OBJECTIVES: To immobilize Candida rugosa lipase in Accurel MP 1000 (CRL-AMP) by physical adsorption in organic medium and apply in the synthesis of wax esters dodecanoyl octadecanoate 1 and hexadecanoyl octadecanoate 2 in a heptane medium, as well as evaluating the stability and recyclability of CRL-AMP in six reaction cycles. RESULTS: The specific activity (Asp) for CRL-AMP was 200 ± 20 U mg-1. Its catalytic activity was 1300 ± 100 U g-1. CRL-AMP was used in the synthesis of esters in heptane medium with a 1:1 acid:alcohol molar ratio at 45 °C and 200 rpm. In synthesis 1, conversion was 62.5 ± 3.9% in 30 min at 10% m v-1 and 56.9 ± 2.8% in 54 min at 5% m v-1; while in synthesis 2, conversion was 79.0 ± 3.9% in 24 min at 10% m v-1, and 46.0 ± 2.4% in 54 min at 5% m v-1. Reuse tests after six consecutive cycles of reaction showed that the biocatalyst retained approximately 50% of its original activity for both reaction systems. CONCLUSIONS: CRL-AMP showed a high potential in the production of wax esters, since it started from low enzymatic load and high specific activities and conversions were obtained, in addition to allowing an increase in stability and recyclability of the prepared biocatalyst.


Assuntos
Ésteres , Lipase , Biocatálise , Candida/metabolismo , Emolientes , Estabilidade Enzimática , Enzimas Imobilizadas/metabolismo , Esterificação , Lipase/metabolismo , Saccharomycetales
8.
Appl Environ Microbiol ; 88(4): e0223721, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-34936835

RESUMO

Multiple studies have found that streptococci have a synergistic relationship with Candida species, but the details of these interactions are still being discovered. Candida species are covered by mannan, a polymer of mannose, which could serve as a carbon source for certain microbes. We hypothesized that streptococci that possess mannan-degrading glycosyl hydrolases would be able to enzymatically cleave mannose residues, which could serve as a primary carbohydrate source to support growth. We analyzed 90 streptococcus genomes to predict the capability of streptococci to transport and utilize mannose and to degrade diverse mannose linkages found on mannan. The genome analysis revealed mannose transporters and downstream pathways in most streptococci, but only <50% of streptococci harbored the glycosyl hydrolases required for mannan degradation. To confirm the ability of streptococci to use mannose or mannan, we grew 6 representative streptococci in a chemically defined medium lacking glucose supplemented with mannose, yeast extract, or purified mannan isolated from Candida and Saccharomyces strains. Although all tested Streptococcus strains could use mannose, Streptococcus salivarius and Streptococcus agalactiae, which did not possess mannan-degrading glycosyl hydrolases, could not use yeast extract or mannan to enhance their growth. In contrast, we found that Streptococcus mitis, Streptococcus parasanguinis, Streptococcus sanguinis, and Streptococcus pyogenes possessed the necessary glycosyl hydrolases to use yeast extract and isolated mannan, which promoted robust growth. Our data indicate that several streptococci are capable of degrading fungal mannans and harvesting mannose for energy. IMPORTANCE This work highlights a previously undescribed aspect of streptococcal Candida interactions. Our work identifies that certain streptococci possess the enzymes required to degrade mannan, and through this mechanism, they can release mannose residues from the cell wall of fungal species and use them as a nutrient source. We speculate that streptococci that can degrade fungal mannan may have a competitive advantage for colonization. This finding has broad implications for human health, as streptococci and Candida are found at multiple body sites.


Assuntos
Candida , Mananas , Candida/metabolismo , Parede Celular/metabolismo , Humanos , Mananas/metabolismo , Manose , Streptococcus/metabolismo
9.
Eur J Med Chem ; 227: 113950, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34731761

RESUMO

Ergosterol exert the important function in maintaining the fluidity and osmotic pressure of fungal cells, and its key biosynthesis enzymes (Squalene epoxidase, SE; 14 α-demethylase, CYP51) displayed the obvious synergistic effects. Therefore, we expected to discover the novel antifungal compounds with dual-target (SE/CYP51) inhibitory activity. In the progress, we screened the different kinds of potent fragments based on the dual-target (CYP51, SE) features, and the method of fragment-based drug discovery (FBDD) was used to guide the construction of three different series of benzodioxane compounds. Subsequently, their chemical structures were synthesized and evaluated. These compounds displayed the obvious biological activity against the pathogenic fungal strains. Notably, target compounds 10a-2 and 22a-2 possessed the excellent broad-spectrum anti-fungal activity (MIC50, 0.125-2.0 µg/mL) and the activity against drug-resistant strains (MIC50, 0.5-2.0 µg/mL). Preliminary mechanism studies have confirmed that these compounds effectively inhibited the dual-target (SE/CYP51) activity, they could cause fungal rupture and death by blocking the bio-synthetic pathway of ergosterol. Further experiments discovered that compounds 10a-2 and 22a-2 also maintained a certain of anti-fungal effect in vivo. In summary, this study not only provided the new dual-target drug design strategy and method, but also discover the potential antifungal compounds.


Assuntos
Inibidores de 14-alfa Desmetilase/farmacologia , Antifúngicos/farmacologia , Derivados de Benzeno/farmacologia , Candida/efeitos dos fármacos , Dioxanos/farmacologia , Esterol 14-Desmetilase/metabolismo , Inibidores de 14-alfa Desmetilase/síntese química , Inibidores de 14-alfa Desmetilase/química , Antifúngicos/síntese química , Antifúngicos/química , Derivados de Benzeno/síntese química , Derivados de Benzeno/química , Candida/metabolismo , Dioxanos/síntese química , Dioxanos/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade
10.
Molecules ; 26(23)2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34885791

RESUMO

The aliphatic heterocycles piperidine and morpholine are core structures of well-known antifungals such as fenpropidin and fenpropimorph, commonly used as agrofungicides, and the related morpholine amorolfine is approved for the treatment of dermal mycoses in humans. Inspired by these lead structures, we describe here the synthesis and biological evaluation of 4-aminopiperidines as a novel chemotype of antifungals with remarkable antifungal activity. A library of more than 30 4-aminopiperidines was synthesized, starting from N-substituted 4-piperidone derivatives by reductive amination with appropriate amines using sodium triacetoxyborohydride. Antifungal activity was determined on the model strain Yarrowia lipolytica, and some compounds showed interesting growth-inhibiting activity. These compounds were tested on 20 clinically relevant fungal isolates (Aspergillus spp., Candida spp., Mucormycetes) by standardized microbroth dilution assays. Two of the six compounds, 1-benzyl-N-dodecylpiperidin-4-amine and N-dodecyl-1-phenethylpiperidin-4-amine, were identified as promising candidates for further development based on their in vitro antifungal activity against Candida spp. and Aspergillus spp. Antifungal activity was determined for 18 Aspergillus spp. and 19 Candida spp., and their impact on ergosterol and cholesterol biosynthesis was determined. Toxicity was determined on HL-60, HUVEC, and MCF10A cells, and in the alternative in vivo model Galleria mellonella. Analysis of sterol patterns after incubation gave valuable insights into the putative molecular mechanism of action, indicating inhibition of the enzymes sterol C14-reductase and sterol C8-isomerase in fungal ergosterol biosynthesis.


Assuntos
Antifúngicos/farmacologia , Ergosterol/metabolismo , Fungos/efeitos dos fármacos , Piperidinas/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Aspergillus/efeitos dos fármacos , Aspergillus/metabolismo , Vias Biossintéticas/efeitos dos fármacos , Candida/efeitos dos fármacos , Candida/metabolismo , Descoberta de Drogas , Fungos/metabolismo , Humanos , Mucorales/efeitos dos fármacos , Mucorales/metabolismo , Micoses/tratamento farmacológico , Micoses/metabolismo , Piperidinas/síntese química , Piperidinas/química , Relação Estrutura-Atividade
11.
Nat Commun ; 12(1): 7317, 2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34916523

RESUMO

Long non-coding RNAs (lncRNAs) constitute a poorly studied class of transcripts with emerging roles in key cellular processes. Despite efforts to characterize lncRNAs across a wide range of species, these molecules remain largely unexplored in most eukaryotic microbes, including yeast pathogens of the Candida clade. Here, we analyze thousands of publicly available sequencing datasets to infer and characterize the lncRNA repertoires of five major Candida pathogens: Candida albicans, Candida tropicalis, Candida parapsilosis, Candida auris and Candida glabrata. Our results indicate that genomes of these species encode hundreds of lncRNAs that show levels of evolutionary constraint intermediate between those of intergenic genomic regions and protein-coding genes. Despite their low sequence conservation across the studied species, some lncRNAs are syntenic and are enriched in shared sequence motifs. We find co-expression of lncRNAs with certain protein-coding transcripts, hinting at potential functional associations. Finally, we identify lncRNAs that are differentially expressed during infection of human epithelial cells for four of the studied species. Our comprehensive bioinformatic analyses of Candida lncRNAs pave the way for future functional characterization of these transcripts.


Assuntos
Candida/genética , Genoma Fúngico , Genômica , RNA Longo não Codificante/genética , Candida/metabolismo , Biologia Computacional , Sequência Conservada , Células Epiteliais , Regulação Fúngica da Expressão Gênica , Humanos , RNA Longo não Codificante/metabolismo , Sintenia , Transcriptoma
12.
Gut Microbes ; 13(1): 1993598, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34793277

RESUMO

Antibiotics are commonly used in the Intensive Care Unit (ICU); however, several studies showed that the impact of antibiotics to prevent infection, multi-organ failure, and death in the ICU is less clear than their benefit on course of infection in the absence of organ dysfunction. We characterized here the compositional and metabolic changes of the gut microbiome induced by critical illness and antibiotics in a cohort of 75 individuals in conjunction with 2,180 gut microbiome samples representing 16 different diseases. We revealed an "infection-vulnerable" gut microbiome environment present only in critically ill treated with antibiotics (ICU+). Feeding of Caenorhabditis elegans with Bifidobacterium animalis and Lactobacillus crispatus, species that expanded in ICU+ patients, revealed a significant negative impact of these microbes on host viability and developmental homeostasis. These results suggest that antibiotic administration can dramatically impact essential functional activities in the gut related to immune responses more than critical illness itself, which might explain in part untoward effects of antibiotics in the critically ill.


Assuntos
Antibacterianos/efeitos adversos , Estado Terminal , Microbioma Gastrointestinal/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Bactérias/patogenicidade , Ácidos e Sais Biliares/metabolismo , Candida/classificação , Candida/efeitos dos fármacos , Candida/metabolismo , Candida/patogenicidade , Farmacorresistência Fúngica/efeitos dos fármacos , Ácidos Graxos Voláteis/metabolismo , Humanos , Infecções/microbiologia , Unidades de Terapia Intensiva , Mariposas
13.
BMC Biotechnol ; 21(1): 58, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635076

RESUMO

BACKGROUND: Published biocatalytic routes for accessing enantiopure 2-phenylpropanol using oxidoreductases afforded maximal product titers of only 80 mM. Enzyme deactivation was identified as the major limitation and was attributed to adduct formation of the aldehyde substrate with amino acid residues of the reductase. RESULTS: A single point mutant of Candida tenuis xylose reductase (CtXR D51A) with very high catalytic efficiency (43·103 s-1 M-1) for (S)-2-phenylpropanal was found. The enzyme showed high enantioselectivity for the (S)-enantiomer but was deactivated by 0.5 mM substrate within 2 h. A whole-cell biocatalyst expressing the engineered reductase and a yeast formate dehydrogenase for NADH-recycling provided substantial stabilization of the reductase. The relatively slow in situ racemization of 2-phenylpropanal and the still limited biocatalyst stability required a subtle adjustment of the substrate-to-catalyst ratio. A value of 3.4 gsubstrate/gcell-dry-weight was selected as a suitable compromise between product ee and the conversion ratio. A catalyst loading of 40 gcell-dry-weight was used to convert 1 M racemic 2-phenylpropanal into 843 mM (115 g/L) (S)-phenylpropanol with 93.1% ee. CONCLUSION: The current industrial production of profenols mainly relies on hydrolases. The bioreduction route established here represents an alternative method for the production of profenols that is competitive with hydrolase-catalyzed kinetic resolutions.


Assuntos
Aldeído Redutase , Candida , Aldeído Redutase/metabolismo , Candida/metabolismo , Cinética , Propanóis , Especificidade por Substrato
14.
Int J Mol Sci ; 22(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34502174

RESUMO

Invasive fungal infections (IFIs) are serious infections that develop in conjunction with neutropenia after chemotherapy for acute leukemia or with hematopoietic stem cell transplantation. Conventionally, empirical antifungal therapy was recommended to treat IFIs for patient safety despite a lack of evidence of fungal infections. However, many studies have indicated that antifungals were not necessary for over half of patients, and several detriments of empirical therapy were noted, e.g., antifungals caused adverse reactions, an increase in drug-resistant fungi was a possibility, and medical costs soared. ß-D-glucan (BDG) is a component of clinically important fungi such as Aspergillus and Candida. The G-test was developed in Japan as a way to measure BDG in serum using a coagulation factor from the blood of the horseshoe crab. Pre-emptive antifungal therapy based upon serodiagnosis with a BDG or galactomannan assay and CT imaging has been introduced. With pre-emptive antifungal therapy, the prognosis is equivalent to that with empirical therapy, and the dose of the antifungal has been successfully reduced. Measurement of BDG has been adopted widely as a method of diagnosing IFIs and is listed in the key guidelines for fungal infections and febrile neutropenia.


Assuntos
Antifúngicos/uso terapêutico , Infecções Fúngicas Invasivas/tratamento farmacológico , beta-Glucanas/análise , Aspergillus/metabolismo , Biomarcadores/análise , Candida/metabolismo , Humanos , Infecções Fúngicas Invasivas/diagnóstico
15.
Appl Environ Microbiol ; 87(18): e0111021, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34232723

RESUMO

Microbial degradation plays an important role in environmental remediation. However, most microorganisms' pollutant-degrading capabilities are weakened due to their entry into a viable but nonculturable (VBNC) state. Although there is some evidence for the VBNC state of pollutant-degrading bacteria, limited studies have been conducted to investigate the VBNC state of pollutant degraders among fungi. In this work, the morphological, physiological, and molecular changes of phenol-degrading yeast strain LN1 exposed to high phenol concentrations were investigated. The results confirmed that Candida sp. strain LN1, which possessed a highly efficient capability of degrading 1,000 mg/liter of phenol as well as a high potential for aromatic compound degradation, entered into the VBNC state after 14 h of incubation with 6,000 mg/liter phenol. Resuscitation of VBNC cells can restore their phenol degradation performance. Compared to normal cells, significant dwarfing, surface damage, and physiological changes of VBNC cells were observed. Molecular analysis indicated that downregulated genes were related to the oxidative stress response, xenobiotic degradation, and carbohydrate and energy metabolism, whereas upregulated genes were related to RNA polymerase, amino acid metabolism, and DNA replication and repair. This report revealed that a pollutant-degrading yeast strain entered into the VBNC state under high concentrations of contaminants, providing new insights into its survival status and bioremediation potential under stress. IMPORTANCE The viable but nonculturable (VBNC) state is known to affect the culturability and activity of microorganisms. However, limited studies have been conducted to investigate the VBNC state of other pollutant degraders, such as fungi. In this study, the VBNC state of a phenol-degrading yeast strain was discovered. In addition, comprehensive analyses of the morphological, physiological, and molecular changes of VBNC cells were performed. This study provides new insight into the VBNC state of pollutant degraders and how they restored the activities that were inhibited under stressful conditions. Enhanced bioremediation performance of indigenous microorganisms could be expected by preventing and controlling the formation of the VBNC state.


Assuntos
Candida/efeitos dos fármacos , Poluentes Ambientais/administração & dosagem , Fenol/administração & dosagem , Biodegradação Ambiental/efeitos dos fármacos , Candida/genética , Candida/crescimento & desenvolvimento , Candida/metabolismo , Relação Dose-Resposta a Droga , Genoma Fúngico , Viabilidade Microbiana/efeitos dos fármacos , Estresse Fisiológico , Sequenciamento Completo do Genoma
16.
Int J Mol Sci ; 22(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068595

RESUMO

Systemic inflammation, from gut translocation of organismal molecules, might worsen uremic complications in acute kidney injury (AKI). The monitoring of gut permeability integrity and/or organismal molecules in AKI might be clinically beneficial. Due to the less prominence of Candida albicans in human intestine compared with mouse gut, C. albicans were orally administered in bilateral nephrectomy (BiN) mice. Gut dysbiosis, using microbiome analysis, and gut permeability defect (gut leakage), which was determined by fluorescein isothiocyanate-dextran and intestinal tight-junction immunofluorescent staining, in mice with BiN-Candida was more severe than BiN without Candida. Additionally, profound gut leakage in BiN-Candida also resulted in gut translocation of lipopolysaccharide (LPS) and (1→3)-ß-D-glucan (BG), the organismal components from gut contents, that induced more severe systemic inflammation than BiN without Candida. The co-presentation of LPS and BG in mouse serum enhanced inflammatory responses. As such, LPS with Whole Glucan Particle (WGP, a representative BG) induced more severe macrophage responses than LPS alone as determined by supernatant cytokines and gene expression of downstream signals (NFκB, Malt-1 and Syk). Meanwhile, WGP alone did not induced the responses. In parallel, WGP (with or without LPS), but not LPS alone, accelerated macrophage ATP production (extracellular flux analysis) through the upregulation of genes in mitochondria and glycolysis pathway (using RNA sequencing analysis), without the induction of cell activities. These data indicated a WGP pre-conditioning effect on cell energy augmentation. In conclusion, Candida in BiN mice accelerated gut translocation of BG that augmented cell energy status and enhanced pro-inflammatory macrophage responses. Hence, gut fungi and BG were associated with the enhanced systemic inflammation in acute uremia.


Assuntos
Injúria Renal Aguda/metabolismo , Candida albicans/metabolismo , Inflamação/sangue , Proteoglicanas/sangue , Injúria Renal Aguda/genética , Injúria Renal Aguda/microbiologia , Animais , Candida/metabolismo , Candida albicans/patogenicidade , Disbiose/sangue , Metabolismo Energético , Humanos , Inflamação/microbiologia , Inflamação/patologia , Inflamação/cirurgia , Lipopolissacarídeos/sangue , Macrófagos/metabolismo , Macrófagos/microbiologia , Macrófagos/patologia , Camundongos , Microbiota/genética , Nefrectomia/efeitos adversos
17.
DNA Res ; 28(3)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34129020

RESUMO

Candida subhashii belongs to the CUG-Ser clade, a group of phylogenetically closely related yeast species that includes some human opportunistic pathogens, such as Candida albicans. Despite being present in the environment, C. subhashii was initially described as the causative agent of a case of peritonitis. Considering the relevance of whole-genome sequencing and analysis for our understanding of genome evolution and pathogenicity, we sequenced, assembled and annotated the genome of C. subhashii type strain. Our results show that C. subhashii presents a highly heterozygous genome and other signatures that point to a hybrid ancestry. The presence of functional pathways for assimilation of hydroxyaromatic compounds goes in line with the affiliation of this yeast with soil microbial communities involved in lignin decomposition. Furthermore, we observed that different clones of this strain may present circular or linear mitochondrial DNA. Re-sequencing and comparison of strains with differential mitochondrial genome topology revealed five candidate genes potentially associated with this conformational change: MSK1, SSZ1, ALG5, MRPL9 and OYE32.


Assuntos
Candida/genética , Núcleo Celular/genética , Genoma Fúngico , Genoma Mitocondrial , Redes e Vias Metabólicas , Fenóis/metabolismo , Candida/metabolismo , Sequenciamento Completo do Genoma
18.
mSphere ; 6(2)2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910989

RESUMO

The polysaccharide chitosan is found in the cell wall of specific cell types in a variety of fungal species where it contributes to stress resistance, or in pathogenic fungi, virulence. Under certain growth conditions, the pathogenic yeast Candida dubliniensis forms a cell type termed a chlamydospore, which has an additional internal layer in its cell wall compared to hyphal or yeast cell types. We report that this internal layer of the chlamydospore wall is rich in chitosan. The ascospore wall of Saccharomyces cerevisiae also has a distinct chitosan layer. As in S. cerevisiae, formation of the chitosan layer in the C. dubliniensis wall requires the chitin synthase CHS3 and the chitin deacetylase CDA2 In addition, three lipid droplet-localized proteins-Rrt8, Srt1, and Mum3-identified in S. cerevisiae as important for chitosan layer assembly in the ascospore wall are required for the formation of the chitosan layer of the chlamydospore wall in C. dubliniensis These results reveal that a conserved machinery is required for the synthesis of a distinct chitosan layer in the walls of these two yeasts and may be generally important for incorporation of chitosan into fungal walls.IMPORTANCE The cell wall is the interface between the fungal cell and its environment and disruption of cell wall assembly is an effective strategy for antifungal therapies. Therefore, a detailed understanding of how cell walls form is critical to identify potential drug targets and develop therapeutic strategies. This study shows that a set of genes required for the assembly of a chitosan layer in the cell wall of S. cerevisiae is also necessary for chitosan formation in a different cell type in a different yeast, C. dubliniensis Because chitosan incorporation into the cell wall can be important for virulence, the conservation of this pathway suggests possible new targets for antifungals aimed at disrupting cell wall function.


Assuntos
Candida/genética , Candida/metabolismo , Parede Celular/metabolismo , Quitosana/metabolismo , Candida/patogenicidade , Parede Celular/genética , Quitina Sintase/genética , Quitina Sintase/metabolismo , Regulação Fúngica da Expressão Gênica , Esporos Fúngicos/genética , Esporos Fúngicos/crescimento & desenvolvimento , Virulência
19.
United European Gastroenterol J ; 9(3): 332-342, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33887125

RESUMO

BACKGROUND: The gut fermentation syndrome (GFS), also known as the endogenous alcohol fermentation syndrome or auto brewery syndrome, is a rare and underdiagnosed medical condition where consumed carbohydrates are converted to alcohol by the microbiota in the gastrointestinal or urinary tract. The symptoms of GFS can have severe impact on patients' wellbeing and can have social and legal consequences. Unfortunately, not much is reported about GFS. The aim of this systematic review was to assess the evidence for GFS, causal micro-organisms, diagnostics, and possible treatments. METHODS: A protocol was developed prior to initiation of the systematic review (PROSPERO 207182). We performed a literature search for clinical studies on 1 September 2020 using PubMed and Embase. We included all clinical studies, including case reports that described the GFS. RESULTS: In total, 17 case reports were included, consisting of 20 patients diagnosed with GFS. The species that caused the GFS included Klebsiella pneumoniae, Candida albicans, C. glabrata, Saccharomyces cerevisiae, C. intermedia, C. parapsilosis, and C. kefyr. CONCLUSIONS: GFS is a rare but underdiagnosed disease in daily practice. The disease is mostly reported by Saccharomyces and Candida genera, and some cases were previously treated with antibiotics. Studies in Nonalcoholic Fatty Liver disease suggest a bacterial origin of endogenous alcohol-production, which might also be causal micro-organisms in GFS. Current treatments for GFS include antibiotics, antifungal medication, low carbohydrate diet, and probiotics. There might be a potential role of fecal microbiota transplant in the treatment of GFS.


Assuntos
Carboidratos da Dieta/metabolismo , Etanol/metabolismo , Fermentação , Microbioma Gastrointestinal/fisiologia , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Viés , Candida/metabolismo , Dieta com Restrição de Carboidratos , Transplante de Microbiota Fecal , Humanos , Klebsiella pneumoniae/metabolismo , Registros Médicos/estatística & dados numéricos , Hepatopatia Gordurosa não Alcoólica/microbiologia , Probióticos/uso terapêutico , Saccharomyces cerevisiae/metabolismo , Síndrome
20.
J Sci Food Agric ; 101(13): 5645-5651, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33740265

RESUMO

BACKGROUND: Esters are indispensable aroma compounds and contribute significantly to the fruity aromas in fermented condiments. The ester synthesis activity and pathways of Bacillus licheniformis, Candida etchellsii, and Zygosaccharomyces rouxii, isolated from Chinese horse bean chili-paste (CHCP), were investigated. Chemical buffer models containing esterification and alcoholysis systems inoculated with extracellular extracts of these three strains were established. RESULTS: The ester synthesis activity of C. etchellsii was stronger than that of the other two strains. Zygosaccharomyces rouxii could synthesize acetate esters via esterification, whereas the biosynthesis pathways of B. licheniformis and C. etchellsii were esterification and alcoholysis. Esterification exhibited relatively high activity at pH 4, whereas alcoholysis activity improved with an increase in the pH from 4 to 8. Candida etchellsii could synthesize C6 -C8 of acetate esters, and its activity improved with the number of alcohol carbon atoms. These three strains could synthesize C10 -C18 of ethyl esters. Their ethyl ester synthesis activity decreased with the aliphatic acid carbon number. CONCLUSION: Candida etchellsii has the potential to be used in CHCP fermentation to accumulate esters and improve flavor compared with the other two strains. This research is helpful in explaining the mechanism of ester synthesis in fermented condiments. © 2021 Society of Chemical Industry.


Assuntos
Bacillus licheniformis/metabolismo , Candida/metabolismo , Ésteres/metabolismo , Aromatizantes/metabolismo , Saccharomycetales/metabolismo , Vicia faba/microbiologia , China , Condimentos/análise , Condimentos/microbiologia , Esterificação , Ésteres/análise , Fermentação , /microbiologia , Aromatizantes/química , Vicia faba/química , Vicia faba/metabolismo
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