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1.
J. Health Biol. Sci. (Online) ; 10(1): 1-6, 01/jan./2022. tab, ilus
Artigo em Inglês | LILACS | ID: biblio-1370924

RESUMO

Objective: to evaluate the molecular interaction of silibinin with the targets ALS3 and SAP5. Methodology: Molecular docking protocols were conducted to analyze the binding interaction of silibinin with ALS3 and SAP5. Results: Eleven interactions of ALS3 with silibinin and four with fluconazole were found, while six interactions were observed of SAP5 with silibinin and four with fluconazole. Conclusion: Molecular docking between silibinin and ALS3 identified important interactions, but no significant interactions were observed with SAP5, even though silibinin can exhibit affinity and interactions with other SAP5 sites.


Objetivo: Avaliar a interação molecular da silibinina com os alvos ALS3 e SAP5. Metodologia: Protocolos de docking molecular foram conduzidos para analisar a interação de ligação da silibinina com ALS3 e SAP5. Resultados: Foram encontradas onze interações de ALS3 com silibinina e quatro com fluconazol, enquanto seis interações foram observadas de SAP5 com silibinina e quatro com fluconazol. Conclusão: Docking molecular entre silibinina e ALS3 identificou interações importantes, mas não foram observadas interações significativas com SAP5, embora a silibinina possa apresentar afinidade e interações com outros sítios SAP5.


Assuntos
Candida albicans , Silimarina , Proteínas , Infecções Fúngicas Invasivas
2.
Klin Lab Diagn ; 67(7): 399-406, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35924770

RESUMO

The aim of the study was to determine the main Candida species isolated from blood of cancer patients, to compare the taxonomic structure of strains obtained from children and adults with candidemia. In total, during the study period, candidemia was microbiologically proven by blood culture in 81 patients (duplicates were excluded). Patients in the intensive care unit (ICU) accounted for 35,8%. The total number of isolates elaborated was 82 strains of 10 Candida species. In general, in the taxonomic structure of candidemias, C. parapsilosis (61.0%) predominates, C. albicans (20.7%) is in the second place, followed by C. glabrata and C. lusitaniae (3.7% each); C. krusei, C. guilliermondii and C. tropicalis (2.4% each). C. parapsilosis was statistically significantly often isolated from blood compared to C. albicans (61.0% versus 20.7%, respectively, p<0.0001). Candidemia was statistically significantly more often detected in adults than in children (63.0% versus 37.0%, respectively, p<0.002). Moreover, in adults, C. parapsilosis was statistically significantly more often isolated from blood than C. albicans (70.6% versus 15.7%, respectively, p<0.0001). In children, there were no significant differences in the frequency of isolation of C. parapsilosis and C. albicans: the proportion of C. parapsilosis was 45.2%, C. albicans - 29.0%. Rare species were identified in 7.8% of cases in adults, and in 12.9% of cases in children without statistical difference (p>0.05). The proportion of Candida non-albicans during the study period was 79.3%, and C. parapsilosis is the main species in this group (76.9%).


Assuntos
Candidemia , Neoplasias , Adulto , Antifúngicos/uso terapêutico , Candida , Candida albicans , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Candidemia/microbiologia , Criança , Humanos , Neoplasias/epidemiologia , Saccharomycetales
3.
Klin Lab Diagn ; 67(7): 407-413, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35924771

RESUMO

The development of mycotic colonization of the base surface with further biodegradation of acrylic plastics is currently of undoubted interest. The oral cavity is a favorable ecological niche for colonization by fungi and their subsequent possible invasion into the epithelium of the oral mucosa. The method of modulation interference laser microscopy is of considerable interest to researchers in medicine in the context of obtaining the necessary information about the morphological characteristics of microbial cells and the microbiome community as a whole during the colonization of a certain ecological niche in the human body. Purpose of the study: to analyze the microrelief of the biofilm of yeast-like fungi of the species Candida albicans of base plastics of the hot type of polymerization using the method of laser modulation interference microscopy. An experimental study was carried out in order to study biofilms of yeast-like fungi of the genus Candida on samples of basic plastics, an image of a biofilm of yeast-like fungi of the species Candida albicans was obtained on the surface of a plastic of a hot type of polymerization (polymethyl methacrylate) in the visualization of the phase portrait, a description of its horizontal and vertical bioprofile. As a result of the research, the heterogeneous structure of the biofilm was determined, due to the different density and accumulation of cells along the surface, the characteristics of the surface were established in accordance with the roughness criteria. The microrelief parameters on a separately arbitrarily selected section line allow one to determine the characteristics of the biofilm in the required area and make it possible to judge the nature of its formation in a certain biological niche.


Assuntos
Candida albicans , Plásticos , Biofilmes , Humanos , Lasers , Microscopia Confocal , Microscopia de Interferência
4.
Front Immunol ; 13: 925821, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935947

RESUMO

Pre-term infants in neonatal intensive care units are vulnerable to fungal sepsis. In this patient population, Candida albicans remains the predominant fungal pathogen causing high morbidity and mortality, despite antifungal therapy. Thus, new preventative/therapeutic strategies against neonatal candidiasis are needed. Previously, we have reported that vaccination with recombinant forms of the C. albicans N-termini of the cell wall proteins Als3 (rAls3p-N) and Hyr1 (rHyr1p-N) protected adult mice from disseminated candidiasis. Further, in a Phase 1b/2a NDV-3A (an rAls3p-N formulated with alum) protected women from recurrent vulvovaginal candidiasis, with anti-Als3p IgG2 isotype being a biomarker for efficacy. Here, we performed a proof of concept study to evaluate if anti-Als3p or anti-Hyr1p antibodies are important for prevention of disseminated candidiasis in neonates. Als3 and Hyr1 antigens when adjuvanted with complete Freund's adjuvant (CFA)/incomplete Freund's adjuvant (IFA) induced a robust antibody response with a ten-fold higher titer of IgG2, than attained by either antigen formulated with alum. Transplacental transfer of these antibodies significantly reduced fungal burden in the kidneys of mice pups, and adoptive transfer of vaccinated mothers' sera into pups displayed similar levels of protection. Neutrophils were found important for this efficacy. Finally, anti-Hyr1 antisera potentiated the activity of fluconazole in protecting from C. albicans infection. Our current studies are the first in the field to emphasize the importance of anti-Als3 and anti-Hyr1 antibodies in preventing neonatal candidiasis. Considering that Candida infections in low birthweight infants is a lethal infection, active and passive vaccination strategies using these antigens could have profound clinical relevance.


Assuntos
Candida albicans , Candidíase , Animais , Animais Recém-Nascidos , Feminino , Proteínas Fúngicas/metabolismo , Humanos , Imunoglobulina G , Camundongos
5.
Front Cell Infect Microbiol ; 12: 935322, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937692

RESUMO

Magnolol, a lignin compound extracted from Magnolia officinalis Cortex, has been found to have prominent antifungal effects against Candida albicans. However, the specific mechanism still remains unclear. Therefore, this study aimed to further explore the inhibition mechanism of magnolol against Candida albicans virulence factors and the related signaling pathways. By an XTT reduction assay, a hyphal formation assay, confocal laser scanning microscopy, transmission electron microscopy, a calcofluor white staining assay, and a cell wall ß-glucan quantitative detection assay, we evaluated the inhibitory effects of magnolol against the adhesion, hyphal formation, biofilm viability, biofilm spatial structure, and cell wall ultrastructure of Candida albicans. Moreover, by RNA sequencing and qRT-PCR, we confirmed the effects of magnolol in inhibiting the gene expression of Candida albicans virulence factors and the related signaling pathways. The results revealed that the adhesion and hyphal formation of Candida albicans were inhibited significantly by magnolol. The viability and spatial structures of Candida albicans biofilms were further weakened. Candida albicans ultrastructure showed partial thinning of cell walls and even rupture, with cytoplasmic leakage. The cell wall intergrity and ß-glucan content were also radically reduced. Moreover, magnolol caused significant inhibition of the expression of Candida albicans adhesion, invasion, hyphal formation, biofilm formation, ß-1,3-glucan synthesis, and hydrolase secretion-related genes, including ALS1, ALS3, EFG1, EAP1, FKS1, FKS2, PLB2, and SAP2. Furthermore, the PKC pathway-related genes (RHO1, PKC1, BCK1, MKK2, MKC1) and Cek1 pathway-related genes (CDC42, CST20, STE11, HST7, CEK1) were also significantly downregulated, indicating that the inhibition of magnolol against Candida albicans virulence factors might be related to PKC and Cek1 MAPK signaling pathways. In conclusion, the findings of this study confirmed the inhibition mechanism of magnolol against Candida albicans virulence factors, which might be related to PKC and Cek1 MAPK pathways, thus laying the theoretical foundation for its clinical antifungal applications.


Assuntos
Candida albicans , beta-Glucanas , Antifúngicos/farmacologia , Compostos de Bifenilo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Lignanas , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Transdução de Sinais , Fatores de Virulência/genética , Fatores de Virulência/farmacologia , beta-Glucanas/metabolismo
6.
Int J Mol Sci ; 23(15)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35955701

RESUMO

Due to (i) the simultaneous presence of Helicobacter pylori (ulcer-induced bacteria) and Candida albicans in the stomach and (ii) the possibility of prokaryotic-eukaryotic endosymbiosis (intravacuolar H. pylori in the yeast cells) under stresses, we tested this symbiosis in vitro and in vivo. To that end, intravacuolar H. pylori were induced by the co-incubation of C. albicans with H. pylori under several stresses (acidic pH, non-H. pylori-enrichment media, and aerobic environments); the results were detectable by direct microscopy (wet mount) and real-time polymerase chain reaction (PCR). Indeed, intravacuolar H. pylori were predominant under all stresses, especially the lower pH level (pH 2-3). Interestingly, the H. pylori (an amoxicillin-sensitive strain) inside C. albicans were protected from the antibiotic (amoxicillin), while extracellular H. pylori were neutralizable, as indicated by the culture. In parallel, the oral administration of intravacuolar H. pylori in mice caused H. pylori colonization in the stomach resulting in gastritis, as indicated by gastric histopathology and tissue cytokines, similar to the administration of free H. pylori (extra-Candida bacteria). In conclusion, Candida protected H. pylori from stresses and antibiotics, and the intravacuolar H. pylori were able to be released from the yeast cells, causing gastric inflammation with neutrophil accumulations.


Assuntos
Gastrite , Infecções por Helicobacter , Helicobacter pylori , Amoxicilina , Animais , Antibacterianos/farmacologia , Candida , Candida albicans , Gastrite/tratamento farmacológico , Gastrite/microbiologia , Infecções por Helicobacter/microbiologia , Camundongos , Vacúolos
7.
Molecules ; 27(15)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35956824

RESUMO

Propolis is very popular for its beneficial health properties, such as antimicrobial activity and antioxidant effects. It is one of the most long-serving traditional medicines to mankind due to its interesting chemical diversity and therapeutic properties. The detailed chemical information of propolis samples is very necessary to guarantee its safety and for it to be accepted into health care systems. The phenolic profile of the hydroethanolic extract was determined using HPLC-DAD, and the antioxidant was evaluated using five complementary methods. Triterpenoids were isolated using column chromatography and characterized using 1H NMR and 13C NMR. The effects of the extract and the isolated compounds on quorum sensing mediated processes and biofilm formation in bacteria were evaluated. Protocatechic acid (40.76 ± 0.82 µg/g), 4-hydroxybenzoic acid (24.04 ± 0.21 µg/g), vanillic acid (29.90 ± 1.05 µg/g), quercetin (43.53 ± 1.10 µg/g), and luteolin (4.44 ± 0.48 µg/g) were identified and quantified. The extract showed good antioxidant activity in the DPPH•, ABTS•+, CUPRAC, and metal chelating assays, and this antioxidant effect was confirmed by cyclic voltammetry. 27-Hydroxymangiferonic acid (1), Ambolic acid (2), and Mangiferonic acid (3) were isolated from anti-quorum sensing activity at MIC, and it was indicated that the most active sample was the extract with inhibition diameter zone of 18.0 ± 1.0 mm, while compounds 1, 2, and 3 had inhibition zones of 12.0 ± 0.5 mm, 9.0 ± 1.0 mm, and 12.3 ± 1.0 mm, respectively. The samples inhibited the P. aeruginosa PA01 swarming motility at the three tested concentrations (50, 75, and 100 µg/mL) in a dose-dependent manner. The propolis extract was able to inhibit biofilm formation by S. aureus, E. coli, P. aeruginosa, C. albicans, and C. tropicalis at MIC concentration. Compound 1 proved biofilm inhibition on S. aureus, L. monocytogenes, E. faecalis, E. coli, and C. tropicalis at MIC and MIC/2; compound 2 inhibited the formation of biofilm at MIC on S. aureus, E. faecalis, E. coli, S. typhi, C. albicans, and C. tropicalis; and compound 3 inhibited biofilm formation on E. faecalis, E. coli, C. albicans, and C. tropicalis and further biofilm inhibition on E. coli at MIC/4 and MIC/8. The studied propolis sample showed important amounts of cycloartane-type triterpene acids, and this indicates that there can be significant intra-regional variation probably due to specific flora within the vicinity. The results indicate that propolis and its compounds can reduce virulence factors of pathogenic bacteria.


Assuntos
Própole , Triterpenos , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Bactérias , Biofilmes , Camarões , Candida albicans , Misturas Complexas/farmacologia , Escherichia coli , Pradaria , Testes de Sensibilidade Microbiana , Fenóis/farmacologia , Própole/química , Própole/farmacologia , Pseudomonas aeruginosa , Staphylococcus aureus , Triterpenos/farmacologia
8.
PLoS One ; 17(8): e0272844, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35947573

RESUMO

Green methods have become vital for sustainable development of the scientific and commercial sphere; however, they can bring new challenges, including the need for detailed characterization and elucidation of efficacy of their products. In this study, green method of silver nanoparticles (AgNPs) production was employed using an extract from grapevine canes. The aim of the study was to contribute to the knowledge about biosynthesized AgNPs by focusing on elucidation of their antifungal efficiency based on their size and/or hypothesized synergy with bioactive substances from Vitis vinifera cane extract. The antifungal activity of AgNPs capped and stabilized with bioactive compounds was tested against the opportunistic pathogenic yeast Candida albicans. Two dispersions of nanoparticles with different morphology (characterized by SEM-in-STEM, DLS, UV-Vis, XRD, and AAS) were prepared by modification of reaction conditions suitable for economical production and their long-term stability monitored for six months was confirmed. The aims of the study included the comparison of the antifungal effect against suspension cells and biofilm of small monodisperse AgNPs with narrow size distribution and large polydisperse AgNPs. The hypothesis of synergistic interaction of biologically active molecules from V. vinifera extracts and AgNPs against both cell forms were tested. The interactions of all AgNPs dispersions with the cell surface and changes in cell morphology were imaged using SEM. All variants of AgNPs dispersions were found to be active against suspension and biofilm cells of C. albicans; nevertheless, surprisingly, larger polydisperse AgNPs were found to be more effective. Synergistic action of nanoparticles with biologically active extract compounds was proven for biofilm cells (MBIC80 20 mg/L of polydisperse AgNPs in extract), while isolated nanoparticles suspended in water were more active against suspension cells (MIC 20 mg/L of polydisperse AgNPs dispersed in water). Our results bring new insight into the economical production of AgNPs with defined characteristics, which were proven to target a specific mode of growth of significant pathogen C. albicans.


Assuntos
Nanopartículas Metálicas , Prata , Antibacterianos/farmacologia , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Biofilmes , Candida albicans/metabolismo , Testes de Sensibilidade Microbiana , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Prata/metabolismo , Prata/farmacologia , Água/metabolismo
9.
Front Immunol ; 13: 950215, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958550

RESUMO

The objective was to determine the effect of 5% boric acid gel on vaginal Candida albicans (CA) infections in mice and its effect on the local immune system (i.e., Th1, Th2, and Th17). Female mice were divided into four groups, with 10 mice in each group. Mycelial suspensions were administered into the vaginal lumen close to the cervix in groups B, F, and M. Mice in group B were given boric acid gel, and group F was treated with fluconazole gel for 30 min every 12 h. Group M was treated with sterile water, and group N was not given treatment. After the seventh day of treatment, each group was observed with the naked eye, and vaginal lavage fluid and vaginal tissue were collected. Expression levels of cytokines were measured using enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry. Periodic acid Schiff (PAS) staining was used to measure the fungi in vaginal tissues. There were no significant changes in group M. In groups B and F, there was less vaginal injury and less exudate, with group B doing better than group F. The numbers of CA colonies were higher in groups B, F, and M than in group N (P < 0.01). There was less vaginal colonization of CA in group B than in group F (P < 0.01). After the seventh day of treatment, levels of IFN-γ, IL-17, IL-6, TGF-ß, IL-4, and IL-10 were significantly greater in groups B, F, and M than in group N (P < 0.001); levels of IFN-γ, IL-17, IL-6, and TGF-ß in groups B and F were higher than those of group M (P < 0.01), while IL-4 and IL-10 levels were significantly lower (P < 0.001). The trends of cytokine increases and decreases were more significant in group B than in group F (P < 0.05). Immunohistochemical results were similar to ELISA results. PAS staining revealed that boric acid inhibited hyphal reproduction. The boric acid significantly reduced the symptoms associated with CA vaginal infection. It inhibited the CA growth, prevented vaginal lesions, promoted the secretion of Th1 and Th17 cytokines, and reduced Th2 cytokines.


Assuntos
Candidíase Vulvovaginal , Candidíase , Animais , Ácidos Bóricos , Candida albicans , Candidíase/tratamento farmacológico , Citocinas/metabolismo , Feminino , Humanos , Interleucina-10/metabolismo , Interleucina-17/farmacologia , Interleucina-4/farmacologia , Interleucina-6/farmacologia , Camundongos , Células Th17 , Fator de Crescimento Transformador beta/farmacologia
10.
Biomed Res Int ; 2022: 5218950, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958807

RESUMO

Nigella sativa (NS) is a plant that has long been utilized in traditional medicine as a treatment for certain diseases. The aim of this work was to valorize the essential oil (EO) of this species by phytochemical analysis and antimicrobial and antioxidant evaluation. EO was extracted by hydrodistillation from the seeds of Nigella sativa (EO-NS). Phytochemical content of EO-NS was evaluated by use of gas chromatography coupled to mass spectrometry (GC-MS/MS). Antioxidant ability was in vitro determined by use of three assays: 2.2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing power (FRAP), and total antioxidant capacity (TAC) relative to two synthetic antioxidants: BHT and quercetin. Antimicrobial effect was evaluated against four clinically important bacterial strains (Staphylococcus aureus, ATCC 6633; Escherichia coli, K12; Bacillus subtilis, DSM 6333; and Proteus mirabilis, ATCC 29906) and against four fungal strains (Candida albicans, ATCC 10231; Aspergillus niger, MTCC 282; Aspergillus flavus, MTCC 9606; and Fusarium oxysporum, MTCC 9913). Fifteen constituents that accounted for the majority of the mass of the EO-NS were identified and quantified by use of GC-MSMS. The main component was O-cymene (37.82%), followed by carvacrol (17.68%), α-pinene (10.09%), trans-sabinene hydrate (9.90%), and 4-terpineol (7.15%). EO-NS exhibited significant antioxidant activity with IC50, EC50, and total antioxidant capacity (TAC) of 0.017 ± 0.0002, 0.1196 ± 0.012, and 114.059 ± 0.97 mg EAA/g, respectively. Additionally, EO-NS exhibited promising antibacterial activity on all strains under investigation, especially on E. coli K12 resulting in inhibition diameter of 38.67 ± 0.58 mm and a minimum inhibitory concentration (MIC) of 1.34 ± 0.00 µg/mL. Also, EO-NS had significant antifungal efficacy, with a percentage of inhibition of 67.45 ± 2.31% and MIC of 2.69 ± 0.00 µg/mL against F. oxysporum, MTCC 9913 and with a diameter of inhibition 42 ± 0.00 mm and MIC of 0.67 ± 0.00 µg/mL against C. albicans. To minimize development of antibiotic-resistant bacteria, EO-NS can be utilized as a natural, alternative to synthetic antibiotics and antioxidants to treat free radicals implicated in microbial infection-related inflammatory reactions.


Assuntos
Anti-Infecciosos , Apiaceae , Carum , Nigella sativa , Óleos Voláteis , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Candida albicans , Escherichia coli , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Compostos Fitoquímicos/farmacologia , Sementes , Espectrometria de Massas em Tandem
11.
Front Cell Infect Microbiol ; 12: 943480, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35959372

RESUMO

Severe Early Childhood Caries (sECC) is a multifactorial disease associated with the occurrence of specific oral microorganisms and other environmental, behavioral, and genetic factors. This study aimed to construct a multivariable model including the occurrence of Candida spp. and selected behavioral factors (length of breastfeeding, serving sweet beverages and beginning of brushing child's teeth) to determine their relationships to the occurrence of sECC. In this case-control study 164 children with sECC and 147 children without dental caries were included. MALDI-TOF MS and multiplex qPCR were used to identify Candida spp. and selected bacteria in dental plaque samples, respectively. A questionnaire on oral hygiene, diet, and children's health was filled in by the parents. The constructed multivariable logistic regression model showed an independent influence of the microbial and behavioral factors in sECC etiopathogenesis. The occurrence of C. albicans and C. dubliniensis was associated with higher odds of sECC development (odds ratio, OR: 9.62 and 16.93, respectively), together with breastfeeding of 6 months or less (OR: 2.71), exposure to sweet beverages (OR: 3.77), and starting to brush child's teeth after the 12th month of age (OR: 4.10), all statistically significant (p < 0.01). Considering the high occurrence of C. albicans and C. dubliniensis in dental plaque in children with sECC, we propose them as "keystone pathogens" and risk factors for sECC. The models showed that presence of specific species of Candida in dental plaque may be a better descriptor of sECC than the mentioned behavioral factors.


Assuntos
Cárie Dentária , Placa Dentária , Candida , Candida albicans , Estudos de Casos e Controles , Criança , Pré-Escolar , Suscetibilidade à Cárie Dentária , Humanos , Streptococcus mutans
12.
Front Cell Infect Microbiol ; 12: 940602, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35959374

RESUMO

Streptococcus mutans and Candida albicans, as the most common bacterium and fungus in the oral cavity respectively, are considered microbiological risk markers of early childhood caries. S. mutans membrane vesicles (MVs) contain virulence proteins, which play roles in biofilm formation and disease progression. Our previous research found that S. mutans MVs harboring glucosyltransferases augment C. albicans biofilm formation by increasing exopolysaccharide production, but the specific impact of S. mutans MVs on C. albicans virulence and pathogenicity is still unknown. In the present study, we developed C. albicans biofilms on the surface of cover glass, hydroxyapatite discs and bovine dentin specimens. The results showed that C. albicans can better adhere to the tooth surface with the effect of S. mutans MVs. Meanwhile, we employed C. albicans biofilm-bovine dentin model to evaluate the influence of S. mutans MVs on C. albicans biofilm cariogenicity. In the S. mutans MV-treated group, the bovine dentin surface hardness loss was significantly increased and the surface morphology showed more dentin tubule exposure and broken dentin tubules. Subsequently, integrative proteomic and metabolomic approaches were used to identify the differentially expressed proteins and metabolites of C. albicans when cocultured with S. mutans MVs. The combination of proteomics and metabolomics analysis indicated that significantly regulated proteins and metabolites were involved in amino acid and carbohydrate metabolism. In summary, the results of the present study proved that S. mutans MVs increase bovine dentin demineralization provoked by C. albicans biofilms and enhance the protein and metabolite expression of C. albicans related to carbohydrate metabolism.


Assuntos
Cárie Dentária , Streptococcus mutans , Animais , Biofilmes , Candida albicans , Metabolismo dos Carboidratos , Bovinos , Pré-Escolar , Humanos , Proteômica , Virulência
13.
Microbiol Res ; 263: 127132, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35940106

RESUMO

Intra-abdominal candidiasis (IAC) occurs due to the direct inoculation of Candida into the sterile peritoneal cavity or leakage of the gastrointestinal tract. An important difference between the two forms of the disease is the presence of fecal material, which is exclusive to the latter condition. However, the influence of fecal material on the prognosis of IAC is still poorly understood. Furthermore, methodologies that use the quantification of fungal load by culture methods have low sensitivity, as they do not adequately show the precocity of the infectious process. Here, we developed a new method to evaluate the aspects of the pathophysiology of IAC, mainly the influence of fecal material on the prognosis of infection, by using C. albicans radiolabeled with technetium-99 m (99 mTc). C. albicans was successfully radiolabeled with 99 mTc (18.5 MBq) using dihydrate stannous chloride (100 µM) as a reducing agent. This binding was stable for 72 h. Viability, yeast-to-hyphae transition, morphology, and antifungal susceptibility were not altered by radiolabeling C. albicans with 99 mTc. The biomass and the fungal load of 99 mTc-C. albicans biofilms were reduced compared to the C. albicans non-radiolabeled after 72 h and 48 h of incubation, respectively. In the IAC model, the fungal load in the biodistribution of 99 mTc-C. albicans and culture assays was higher in animals receiving fungal inoculum without fecal material, suggesting that the presence of this component reduces the invasiveness of the pathogen.


Assuntos
Candida albicans , Candidíase , Animais , Antifúngicos/metabolismo , Candida albicans/metabolismo , Candidíase/diagnóstico por imagem , Candidíase/tratamento farmacológico , Modelos Animais de Doenças , Camundongos , Tecnécio , Distribuição Tecidual
14.
Microbiol Res ; 263: 127146, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35940108

RESUMO

The sensing of environmental conditions such as nutrient availability and the ability to adapt and respond to changing conditions are crucial for the survival of living organisms. Evidence from several organisms have revealed that some metabolic enzymes act as sensors of nutrient status and regulate the expression of sets of genes required for nutrients utilization and condition specific environmental adaptation. Thus metabolic enzymes regulate the signaling pathway by acting as transcriptional regulators and providing required metabolites. The commensal yeast, Candida albicans has recently emerged as a model system for understanding the N-acetylglucosamine (GlcNAc) signaling pathway in eukaryotes. GlcNAc kinase (Hxk1), the first enzyme of the catabolic cascade, has been shown to perform several functions such as regulation of gene expression and regulation of the metabolic status of the cell thereby resulting in a change in cell morphology (yeast-hyphal transition, white-opaque switching), metabolic gene expression, synthesis of metabolic precursors, induction of glycolytic flux rate and biofilm formation. Here, in this review we have discussed various roles of Hxk1that have not been reported in other organisms previously. The enzyme exhibits dynamic changes in subcellular localization consistent with its expanded functions inside the cell. Thus Hxk1 in C. albicans orchestrates several dynamic cellular processes and this signaling system can act as a paradigm to understand the cell fate and metabolic specialization in other eukaryotes too. Still, the molecular cues involved in Hxk1 mediating functions are yet to be unveiled; the relationship between Hxk1 sensing and its signaling effects is also not understood yet.


Assuntos
Candida albicans , Regulação Fúngica da Expressão Gênica , Acetilglucosamina/genética , Candida albicans/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo
15.
Front Cell Infect Microbiol ; 12: 890839, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909961

RESUMO

Although it is widely recognized that disruption of ALS3 reduces the invasion of Candida albicans germ tubes into mammalian oral epithelial cells, the mechanism of this interaction was unexplored. C. albicans strains with structurally informed mutations to remove adhesive activity of the peptide-binding cavity (PBC) or aggregative activity mediated by the amyloid-forming region (AFR) were assessed for their ability to invade cultured human oropharyngeal epithelial cells. Initial assays utilized untreated fungal and epithelial cells. Subsequent work used epithelial cells treated with cytochalasin D and C. albicans cells treated with thimerosal to investigate invasion mediated by active penetration of germ tubes and epithelial cell induced endocytosis, respectively. Results demonstrated the importance of the PBC for the invasion process: loss of PBC function resulted in the same reduced-invasion phenotype as a C. albicans strain that did not produce Als3 on its surface. Invasion via active penetration was particularly compromised without PBC function. Loss of AFR function produced a wild-type phenotype in the untreated and thimerosal-treated invasion assays but increased invasion in cytochalasin D-treated epithelial cells. In previous work, reduced AFR-mediated Als3 aggregation increased C. albicans adhesion to cultured epithelial cell monolayers, presumably via increased PBC accessibility for ligand binding. Collectively, results presented here demonstrate that Als3 PBC-mediated adhesion is integral to its invasive function. These new data add to the mechanistic understanding of the role of Als3 in C. albicans invasion into mammalian oral epithelial cells.


Assuntos
Candida albicans , Proteínas Fúngicas , Animais , Candida albicans/genética , Citocalasina D/metabolismo , Citocalasina D/farmacologia , Células Epiteliais/microbiologia , Proteínas Fúngicas/metabolismo , Humanos , Mamíferos/metabolismo , Peptídeos/metabolismo , Timerosal/metabolismo
16.
Arch Microbiol ; 204(8): 537, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913539

RESUMO

This study was designed to evaluate the antimicrobial, antioxidant, and cytotoxic potentials of the marine actinomycetes spp. isolated from the Red Sea water, Hurghada, Egypt. Out of 80 actinomycetes isolates, one isolate AW6 was selected based on its antioxidant activity (IC50 about 5.24 µg/mL which scavenged 91% of formed DPPH free radicals) and antimicrobial potential against E. coli, S. aureus, B. subtilis, and P. aeruginosa, A. niger, and C. albicans. The strain was identified based on phenotypic and genotypic analysis, and deposited in the GenBank with accession number OK090864.1. Cultivation of the selected strain on rice, chromatographic purification, and structural elucidation led to the isolation of two compounds C1: umbelliferone, and C2: 1-methoxy-3-methyl-8-hydroxy-anthraquinone. The antimicrobial activity of the obtained compounds showed that C1 and C2 have low antibacterial activity toward S. aureus and E. coli with no pronounced activity toward P. aeruginosa, C. albicans, and A. niger. Additionally, the antioxidant activity of C1 and C2 revealed that C2 has a good antioxidant activity, with DPPH scavenging activity reaching (55.25%), followed by C1 (30.20%). Moreover, both compounds displayed anti-Gyr-B enzyme activity with IC50 value of (3.79 ± 0.21 µM) for C1, and (IC50 = 13 ± 0.71 µM) for C2. The ADME-related physicochemical properties of the obtained compound were predicted using SwissADME web tools and the ProToxii webserver was used to estimate in silico toxicity.


Assuntos
Anti-Infecciosos , Staphylococcus aureus , Actinomyces , Antibacterianos/química , Anti-Infecciosos/química , Antioxidantes/química , Antioxidantes/farmacologia , Candida albicans , Escherichia coli/genética , Escherichia coli/metabolismo , Pseudomonas aeruginosa/metabolismo , Staphylococcus aureus/metabolismo
17.
Front Immunol ; 13: 959740, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967437

RESUMO

Recurrent vulvovaginal candidiasis (RVVC) and vulvovaginal candidiasis (RVVC) are one of the most common gynecological infections, primarily caused by Candida species. Although risk factors of RVVC and VVC have been identified in many studies, antifungal immunological mechanisms are still not fully understood. We performed a 1-year prospective study in a local hospital to monitor 98 patients clinically diagnosed with gynecological Candida infection. The results showed that 20.41% (20/98) are with RVVC, and 79.59% (78/98) patients have VVC. C. albicans accounts for 90% and 96.1% of all strains isolated collected from RVVC and VVC patients, respectively. Antifungal susceptibility testing showed no significant difference in Candida species between RVVC and VVC patients. However, the serum levels of IFN-γ, TNF-α, and IL-17F in the RVVC group were significantly lower than those of the VVC group, while IL-4, IL-6, and IL-10 were higher in the RVVC patients than VVC patients. IL-17A and IL-2 levels were comparable between the two groups. Taken together, our results suggest that the host-immune responses, especially Th1/2 immunity, may play important roles in prognosis of RVVC and VVC.


Assuntos
Candidíase Vulvovaginal , Antifúngicos , Candida , Candida albicans , Feminino , Humanos , Imunidade , Estudos Prospectivos , Recidiva
18.
BMC Oral Health ; 22(1): 350, 2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-35964034

RESUMO

BACKGROUND: To investigate the effect of ficin, a type of proteases, on Candida albicans (C. albicans) biofilm, including forming and pre-formed biofilms. METHODS: Crystal violet tests together with colony forming unit (CFU) counts were used to detect fungal biofilm biomass. Live/dead staining of biofilms observed by confocal laser scanning microscopy was used to monitor fungal activity. Finally, gene expression of C. albicans within biofilms was assessed by qRT-PCR. RESULTS: According to our results, biofilm biomass was dramatically reduced by ficin in both biofilm formation and pre-formed biofilms, as revealed by the crystal violet assay and CFU count (p < 0.05). Fungal activity in biofilm formation and pre-formed biofilms was not significantly influenced by ficin according to live/dead staining. Fungal polymorphism and biofilm associated gene expression were influenced by ficin, especially in groups with prominent antibiofilm effects. CONCLUSIONS: In summary, ficin effectively inhibited C. albicans biofilm formation and detached its preformed biofilm, and it might be used to treat C. albicans biofilm associated problems.


Assuntos
Candida albicans , Ficina , Biofilmes , Ficina/farmacologia , Violeta Genciana/farmacologia , Humanos , Microscopia Confocal
19.
Eur J Med Chem ; 240: 114609, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35932582

RESUMO

The prevalence of multidrug resistance has been increasingly witnessed during the past few decades. Resistance of human pathogenic fungi against the currently available antifungal agents has increased the frequency of fungal infections and associated mortality rates. The discovery of novel lead antifungal agents is important to challenge multidrug resistance. The present study examined the antifungal potential of chemically synthesized ß-Nitrostyrene derivatives. Among the eight ß-Nitrostyrene derivatives used in this study, SS45, SS46 and SS47 showed strong antifungal potential. The results show that ß-Nitrostyrene derivatives inhibited the growth of different species of human pathogenic Candida, particularly the highly prevalent C. albicans, C. glabrata and the emerging pathogenic C. auris species. Moreover, ß-Nitrostyrene derivatives also show strong antifungal activities against drug-resistant clinical isolates and drug transporter overexpressing fungal species. The drug susceptibility assays revealed that ß-Nitrostyrene derivatives are fungicidal and show the synergy of action when combined with antifungal drugs caspofungin and fluconazole. The transcriptomic study performed on C. albicans in the presence of ß-Nitrostyrene derivatives revealed the differential expression of genes related to cell wall metabolism. Mechanistically, ß-Nitrostyrene derivatives impact cell wall morphology, enhance ROS generation and modulate drug efflux. Collectively this study reveals that ß-Nitrostyrene derivatives have strong antifungal potential with a particular mode of activity similar to known cell wall perturbing antifungal agents and thus can be exploited as promising potential antifungal agents for further studies.


Assuntos
Antifúngicos , Fluconazol , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans , Parede Celular , Farmacorresistência Fúngica , Fluconazol/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Estirenos
20.
Artigo em Inglês | MEDLINE | ID: mdl-35954766

RESUMO

The aim of this study was to determine the effect of humic acid on the growth and metabolism of Candida albicans, a common waterborne pathogenic yeast. At 10-20 mg/L, humic acid caused the greatest increase in biomass and compactness of proteins and monosaccharides, both in cells and in extracellular secretion of the yeast. At higher humic acid concentrations (40-80 mg/L), C. albicans cells still had higher protein levels compared to control, but showed reduced levels of metabolites and inhibited growth, and a significant increase in the activity of antioxidant enzymes, indicating a toxic effect of the humic acid. The increase in protein content in the cells of C. albicans combined with an increase in the activity of antioxidant enzymes may indicate that the studied yeast excels in conditions of high water enrichment with low availability of organic matter. This indicates that Candida albicans is capable of breaking down organic matter that other microorganisms cannot cope with, and for this reason, this yeast uses carbon sources that are not available to other microorganisms. This indicates that this fungus plays an important role in the organic carbon sphere to higher trophic levels, and is common in water polluted with organic matter.


Assuntos
Candida albicans , Substâncias Húmicas , Antioxidantes/metabolismo , Carbono/metabolismo , Polônia , Água/metabolismo
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