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1.
J Med Microbiol ; 73(7)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38979984

RESUMO

Introduction. The development of new antifungal drugs has become a global priority, given the increasing cases of fungal diseases together with the rising resistance to available antifungal drugs. In this scenario, drug repositioning has emerged as an alternative for such development, with advantages such as reduced research time and costs.Gap statement. Propafenone is an antiarrhythmic drug whose antifungal activity is poorly described, being a good candidate for further study.Aim. This study aims to evaluate propafenone activity against different species of Candida spp. to evaluate its combination with standard antifungals, as well as its possible action mechanism.Methodology. To this end, we carried out tests against strains of Candida albicans, Candida auris, Candida parapsilosis, Candida tropicalis, Candida glabrata and Candida krusei based on the evaluation of the MIC, minimum fungicidal concentration and tolerance level, along with checkerboard and flow cytometry tests with clinical strains and cell structure analysis by scanning electron microscopy (SEM).Results. The results showed that propafenone has a 50% MIC ranging from 32 to 256 µg ml-1, with fungicidal activity and positive interactions with itraconazole in 83.3% of the strains evaluated. The effects of the treatments observed by SEM were extensive damage to the cell structure, while flow cytometry revealed the apoptotic potential of propafenone against Candida spp.Conclusion. Taken together, these results indicate that propafenone has the potential for repositioning as an antifungal drug.


Assuntos
Antifúngicos , Candida , Testes de Sensibilidade Microbiana , Propafenona , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Propafenona/farmacologia , Humanos , Itraconazol/farmacologia , Sinergismo Farmacológico , Farmacorresistência Fúngica/efeitos dos fármacos , Candidíase/microbiologia , Candidíase/tratamento farmacológico , Reposicionamento de Medicamentos
2.
Curr Microbiol ; 81(9): 271, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012492

RESUMO

Probiotics and prebiotics have been considered as alternative approaches for promoting health. This study aimed to investigate the anticandidal potential of various probiotic Lactobacillus strains and their cell-free supernatants (CFSs). The study assessed the impact of inulin and some fruits as prebiotics on the growth of selected probiotic strains in relation to their anticandidal activity, production of short-chain fatty acids, total phenolic content, and antioxidant activity. Results revealed variations in anticandidal activity based on the specific strains and forms of probiotics used. Non-adjusted CFSs were the most effective against Candida strains, followed by probiotic cells and adjusted CFSs (pH 7). Lacticaseibacillus rhamnosus SD4, L. rhamnosus SD11 and L. rhamnosus GG displayed the strongest anticandidal activity. Non-adjusted CFSs from L. rhamnosus SD11, L. rhamnosus SD4 and L. paracasei SD1 exhibited notable anticandidal effects. The adjusted CFSs of L. rhamnosus SD11 showed the highest anticandidal activity against all non-albicans Candida (NAC) strains, whereas the others were ineffective. Supplementation of L. rhamnosus SD11 with prebiotics, particularly 2% (w/v) mangosteen, exhibited positive results in promoting probiotic growth, short-chain fatty acids production, total phenolic contents, and antioxidant activity, and the subsequent enhancing anticandidal activity against both C. albicans and NAC strains compared to conditions without prebiotics. In conclusion, both live cells and CFSs of tested strains, particularly L. rhamnosus SD11, exhibited the best anticandidal activity. Prebiotics supplementation, especially mangosteen, enhanced probiotic growth and beneficial metabolites against Candida growth. These finding suggested that probiotics and prebiotic supplementation may be an effective alternative treatment for Candida infections.


Assuntos
Lactobacillus , Prebióticos , Probióticos , Probióticos/farmacologia , Lactobacillus/metabolismo , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Antioxidantes/farmacologia , Inulina/farmacologia , Antifúngicos/farmacologia , Ácidos Graxos Voláteis/metabolismo , Lacticaseibacillus rhamnosus/metabolismo , Fenóis/farmacologia
3.
PLoS One ; 19(6): e0305405, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38889118

RESUMO

Syzigium aromaticum essential oil (EO), eugenol, and ß-caryophyllene were evaluated regarding antifungal, antibiofilm, and in vitro toxicity. Additionally, in vivo toxicity of EO was observed. Anti-Candida activity was assessed through broth microdilution assay for all compounds. Time-kill assay (0, 1, 10, 30 min, 1, 2, and 4 h) was used to determine the influence of EO and eugenol on Candida Growth kinetics. Thereafter, both compounds were evaluated regarding their capacity to act on a biofilm formation and on mature biofilm, based on CFU/ml/g of dry weight. Cell Titer Blue Viability Assay was used for in vitro cytotoxicity, using oral epithelial cells (TR146) and human monocytes (THP-1). Lastly, Galleria mellonella model defined the EO in vivo acute toxicity. All compounds, except ß-cariofilene (MIC > 8000 µg/ml), presented antifungal activity against Candida strains (MIC 500-1000 µg/ml). The growth kinetics of Candida was affected by the EO (5xMIC 30 min onward; 10xMIC 10 min onward) and eugenol (5xMIC 10 min onward; 10xMIC 1 min onward). Fungal viability was also affected by 5xMIC and 10xMIC of both compounds during biofilm formation and upon mature biofilms. LD50 was defined for TR146 and THP1 cells at, respectively, 59.37 and 79.54 µg/ml for the EO and 55.35 and 84.16 µg/ml for eugenol. No sign of toxicity was seen in vivo up to 10mg/ml (20 x MIC) for the EO. S. aromaticum and eugenol presented antifungal and antibiofilm activity, with action on cell growth kinetics. In vivo acute toxicity showed a safe parameter for the EO up to 10 mg/ml.


Assuntos
Antifúngicos , Biofilmes , Candida , Eugenol , Testes de Sensibilidade Microbiana , Óleos Voláteis , Syzygium , Óleos Voláteis/farmacologia , Óleos Voláteis/toxicidade , Humanos , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Syzygium/química , Antifúngicos/farmacologia , Antifúngicos/toxicidade , Animais , Eugenol/farmacologia , Eugenol/toxicidade , Linhagem Celular
4.
J Environ Manage ; 362: 121351, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38838535

RESUMO

In this study, the growth of yeast and yeast-like fungi in the liquid digestate from vegetable wastes was investigated in order to remove nutrients and organic pollutants, and for their application as co-culture members with green microalgae. The studied yeast strains were characterized for their assimilative and enzymatic profiles as well as temperature requirements. In the first experimental stage, the growth dynamics of each strain were determined, allowing to select the best yeasts for further studies. In the subsequent stage, the ability of selectants to remove organic pollutants was assessed. Different cultivation media containing respectively 1:3, 1:1, 3:1 vol ratio of liquid digestate and the basal minimal medium were used. Among all tested yeast strains, Rhodotorula mucilaginosa DSM 70825 showed the most promising results, demonstrating the highest potential for removing organic substrates and nutrients. Depending on the medium, this strain achieved 50-80% sCOD, 45-60% tVFAs, 21-45% TN, 33-52% PO43- reduction rates. Similar results were obtained for the strain Candida sp. OR687571. The high nutrient and organics removal efficiency by these yeasts could likely be linked to their ability to assimilate xylose (being the main source of carbon in the liquid digestate). In culture media containing liquid digestate, both yeast strains achieved good viability and proliferation potential. In the liquid digestate medium, R. mucilaginosa and Candida sp. showed vitality at the level of 51.5% and 45.0%, respectively. These strains seem to be a good starting material for developing effective digestate treatment strategies involving monocultures and/or consortia with other yeasts or green microalgae.


Assuntos
Técnicas de Cocultura , Microalgas , Leveduras , Microalgas/crescimento & desenvolvimento , Microalgas/metabolismo , Leveduras/metabolismo , Leveduras/crescimento & desenvolvimento , Rhodotorula/metabolismo , Rhodotorula/crescimento & desenvolvimento , Nutrientes/metabolismo , Biodegradação Ambiental , Candida/crescimento & desenvolvimento , Candida/metabolismo
5.
J Insect Sci ; 24(3)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38713543

RESUMO

The black soldier fly, Hermetia illucens L. (Diptera: Stratiomyidae), is commonly used for organic waste recycling and animal feed production. However, the often inadequate nutrients in organic waste necessitate nutritional enhancement of black soldier fly larvae, e.g., by fungal supplementation of its diet. We investigated the amino acid composition of two fungi, Candida tropicalis (Castell.) Berkhout (Saccharomycetales: Saccharomycetaceae) and Pichia kudriavzevii Boidin, Pignal & Besson (Saccharomycetales: Pichiaceae), from the black soldier fly gut, and commercial baker's yeast, Saccharomyces cerevisiae Meyen ex E.C. Hansen (Saccharomycetales: Saccharomycetaceae), and their effects on larval growth and hemolymph metabolites in fifth-instar black soldier fly larvae. Liquid chromatography-mass spectrometry was used to study the effect of fungal metabolites on black soldier fly larval metabolism. Amino acid analysis revealed significant variation among the fungi. Fungal supplementation led to increased larval body mass and differential metabolite accumulation. The three fungal species caused distinct metabolic changes, with each over-accumulating and down-accumulating various metabolites. We identified significant alteration of histidine metabolism, aminoacyl-tRNA biosynthesis, and glycerophospholipid metabolism in BSF larvae treated with C. tropicalis. Treatment with P. kudriavzevii affected histidine metabolism and citrate cycle metabolites, while both P. kudriavzevii and S. cerevisiae treatments impacted tyrosine metabolism. Treatment with S. cerevisiae resulted in down-accumulation of metabolites related to glycine, serine, and threonine metabolism. This study suggests that adding fungi to the larval diet significantly affects black soldier fly larval metabolomics. Further research is needed to understand how individual amino acids and their metabolites contributed by fungi affect black soldier fly larval physiology, growth, and development, to elucidate the interaction between fungal nutrients and black soldier fly physiology.


Assuntos
Dípteros , Hemolinfa , Larva , Animais , Larva/crescimento & desenvolvimento , Larva/metabolismo , Dípteros/metabolismo , Dípteros/crescimento & desenvolvimento , Hemolinfa/metabolismo , Pichia/metabolismo , Saccharomyces cerevisiae/metabolismo , Aminoácidos/metabolismo , Dieta , Saccharomycetales/metabolismo , Ração Animal/análise , Candida/metabolismo , Candida/crescimento & desenvolvimento
6.
Arch Microbiol ; 206(6): 257, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734773

RESUMO

There is a growing imperative for research into alternative compounds for the treatment of the fungal infections. Thus, many studies have focused on the analysis of antifungal proteins and peptides from different plant sources. Among these molecules are protease inhibitors (PIs). Previously, PIs present in the peptide-rich fractions called PEF1, PEF2 and PEF3 were identified from Capsicum chinense seeds, which have strong activity against phytopathogenic fungi. The aim of this study was to evaluate the mechanism of action and antimicrobial activity of PIs from PEF2 and PEF3 on the growth of yeasts of the genus Candida. In this work, analyses of their antimicrobial activity and cell viability were carried out. Subsequently, the mechanism of action by which the PIs cause the death of the yeasts was evaluated. Cytotoxicity was assessed in vitro by erythrocytes lysis and in vivo in Galleria mellonella larvae. PEF2 and PEF3 caused 100% of the growth inhibition of C. tropicalis and C. buinensis. For C. albicans inhibition was approximately 60% for both fractions. The PEF2 and PEF3 caused a reduction in mitochondrial functionality of 54% and 46% for C. albicans, 26% and 30% for C. tropicalis, and 71% and 68% for C. buinensis, respectively. These fractions induced morphological alterations, led to membrane permeabilization, elevated ROS levels, and resulted in necrotic cell death in C. tropicalis, whilst demonstrating low toxicity toward host cells. From the results obtained here, we intend to contribute to the understanding of the action of PIs in the control of fungal diseases of medical importance.


Assuntos
Antifúngicos , Candida , Inibidores de Proteases , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Inibidores de Proteases/farmacologia , Testes de Sensibilidade Microbiana , Animais , Capsicum/microbiologia , Espécies Reativas de Oxigênio/metabolismo , Sementes/crescimento & desenvolvimento , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Eritrócitos/efeitos dos fármacos , Larva/microbiologia , Larva/crescimento & desenvolvimento , Larva/efeitos dos fármacos
7.
World J Gastroenterol ; 30(16): 2281-2284, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38690016

RESUMO

The following are our views regarding the "letter to the editor" (Helicobacter is preserved in yeast vacuoles! Does Koch's postulates confirm it?) by Alipour and Gaeini, and the response "letter to the editor" (Candida accommodates non-culturable Helicobacter pylori in its vacuole-Koch's postulates aren't applicable) by Siavoshi and Saniee. Alipour and Gaeini rejected the methods, results, discussion, and conclusions summarized in a review article by Siavoshi and Saniee. The present article reviews and discusses evidence on the evolutionary adaptation of Helicobacter pylori (H. pylori) to thrive in Candida cell vacuoles and concludes that Candida could act as a Trojan horse, transporting potentially infectious H. pylori into the stomach of humans.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Helicobacter pylori/patogenicidade , Humanos , Infecções por Helicobacter/microbiologia , Candida/fisiologia , Candida/crescimento & desenvolvimento , Candida/patogenicidade , Vacúolos/microbiologia , Vacúolos/metabolismo , Estômago/microbiologia , Mucosa Gástrica/microbiologia
8.
Microb Pathog ; 191: 106665, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38685359

RESUMO

Fungal infections caused by Candida species pose a serious threat to humankind. Antibiotics abuse and the ability of Candida species to form biofilm have escalated the emergence of drug resistance in clinical settings and hence, rendered it more difficult to treat Candida-related diseases. Lethal effects of Candida infection are often due to inefficacy of antimicrobial treatments and failure of host immune response to clear infections. Previous studies have shown that a combination of riboflavin with UVA (riboflavin/UVA) light demonstrate candidacidal activity albeit its mechanism of actions remain elusive. Thus, this study sought to investigate antifungal and antibiofilm properties by combining riboflavin with UVA against Candida albicans and non-albicans Candida species. The MIC20 for the fluconazole and riboflavin/UVA against the Candida species tested was within the range of 0.125-2 µg/mL while the SMIC50 was 32 µg/mL. Present findings indicate that the inhibitory activities exerted by riboflavin/UVA towards planktonic cells are slightly less effective as compared to controls. However, the efficacy of the combination towards Candida species biofilms showed otherwise. Inhibitory effects exerted by riboflavin/UVA towards most of the tested Candida species biofilms points towards a variation in mode of action that could make it an ideal alternative therapeutic for biofilm-related infections.


Assuntos
Antifúngicos , Biofilmes , Candida albicans , Candida , Testes de Sensibilidade Microbiana , Riboflavina , Raios Ultravioleta , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Biofilmes/efeitos da radiação , Riboflavina/farmacologia , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Plâncton/efeitos dos fármacos , Fluconazol/farmacologia , Humanos
9.
Molecules ; 27(4)2022 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-35209036

RESUMO

Marine microalgae and cyanobacteria are sources of diverse bioactive compounds with potential biotechnological applications in food, feed, nutraceutical, pharmaceutical, cosmetic and biofuel industries. In this study, five microalgae, Nitzschia sp. S5, Nanofrustulum shiloi D1, Picochlorum sp. D3, Tetraselmis sp. Z3 and Tetraselmis sp. C6, and the cyanobacterium Euhalothece sp. C1 were isolated from the Adriatic Sea and characterized regarding their growth kinetics, biomass composition and specific products content (fatty acids, pigments, antioxidants, neutral and polar lipids). The strain Picochlorum sp. D3, showing the highest specific growth rate (0.009 h-1), had biomass productivity of 33.98 ± 0.02 mg L-1 day-1. Proteins were the most abundant macromolecule in the biomass (32.83-57.94%, g g-1). Nanofrustulum shiloi D1 contained significant amounts of neutral lipids (68.36%), while the biomass of Picochlorum sp. D3, Tetraselmis sp. Z3, Tetraselmis sp. C6 and Euhalothece sp. C1 was rich in glycolipids and phospholipids (75%). The lipids of all studied microalgae predominantly contained unsaturated fatty acids. Carotenoids were the most abundant pigments with the highest content of lutein and neoxanthin in representatives of Chlorophyta and fucoxanthin in strains belonging to the Bacillariophyta. All microalgal extracts showed antioxidant activity and antimicrobial activity against Gram-negative E. coli and S. typhimurium and Gram-positive S. aureus.


Assuntos
Anti-Infecciosos , Antioxidantes , Aspergillus niger/crescimento & desenvolvimento , Bactérias/crescimento & desenvolvimento , Biomassa , Candida/crescimento & desenvolvimento , Clorófitas , Ácidos Graxos Insaturados/química , Microalgas , Pigmentos Biológicos , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Clorófitas/química , Clorófitas/crescimento & desenvolvimento , Ácidos Graxos Insaturados/isolamento & purificação , Ácidos Graxos Insaturados/farmacologia , Microalgas/química , Microalgas/crescimento & desenvolvimento , Oceanos e Mares , Pigmentos Biológicos/química , Pigmentos Biológicos/isolamento & purificação , Pigmentos Biológicos/farmacologia
10.
Biomed Pharmacother ; 143: 112218, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34649348

RESUMO

Oral candidiasis is frequently associated with Candida biofilms. Biofilms are microbial communities related to persistent, recalcitrant and difficult to-treat infections. Conventional treatments are not sufficient to overcome biofilm-associated candidiasis; thus, the search of new antifungal compounds is necessary. In the current study, we have evaluated the effect of three phytocompounds, carvacrol, cinnamaldehyde and thymol, against Candida planktonic and sessile cells. Reduction in biofilm biomass and metabolic activity was assessed during adhesion and mature biofilm phases. Candida albicans was the most biofilm-producing Candida species. All phytocompounds tested were fungicidal against Candida planktonic cells. Cinnamaldehyde was the most active in inhibiting biofilm adhesion, but carvacrol and thymol significantly reduced both mature biofilm biomass and metabolic activity. These results highlight the role of cinnamaldehyde, carvacrol and thymol as promising alternatives for the treatment of candidiasis due to their antibiofilm capacities, and stress the necessity to continue studies on their safety, toxicity and pharmacodynamics and pharmacokinetics.


Assuntos
Acroleína/análogos & derivados , Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Candidíase Bucal/tratamento farmacológico , Cimenos/farmacologia , Timol/farmacologia , Acroleína/farmacologia , Biofilmes/crescimento & desenvolvimento , Candida/crescimento & desenvolvimento , Candidíase Bucal/microbiologia , Testes de Sensibilidade Microbiana
11.
Molecules ; 26(19)2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34641363

RESUMO

Gui Zhen Cao is an herbal formulation that has been documented in Chinese traditional medicine as a remedy for diarrhea, dysentery, inflammation, and toxicity. The sources of this formulation (Bidens pilosa L., Bidens biternata (Lour.) Merr. & Sherff, Bidens bipinnata L.) are also listed in ethnomedicinal reports all over the world. In this study, all these plants are tested for in vitro anticandida activity. A quantitative evaluation of the phytochemicals in all these plants indicated that their vegetative parts are rich in tannins, saponins, oxalates, cyanogenic glycoside and lipids; moreover, the roots have high percentages of alkaloids, flavonoids, and phenols. The results indicated significant anticandida activity, especially for the hexane extract of B. bipinnata leaves which inhibited C. albicans (42.54%), C. glabrata (46.98%), C. tropicalis (50.89%), C. krusei (40.56%), and C. orthopsilosis (50.24%). The extract was subjected to silica gel chromatography and 220 fractions were obtained. Purification by High Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD) and Gas Chromatography tandem Mass Spectrometry (GC-MS/MS) analysis led to the identification of two anticandida compounds: dehydroabietic and linoleic acid having an inhibition of 85 and 92%, respectively.


Assuntos
Bidens/química , Candida/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Flavonoides/farmacologia , Cromatografia Gasosa-Espectrometria de Massas/métodos , Extratos Vegetais/farmacologia , Candida/crescimento & desenvolvimento , Espectrometria de Massas em Tandem/métodos
12.
Molecules ; 26(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34641405

RESUMO

The treatment of benzylidenemalononitriles with phenylhydrazines in refluxing ethanol did not provide pyrazole derivatives, but instead furnished hydrazones. The structure of hydrazones was secured by X-ray analysis. The chemical proof was also obtained by direct reaction of 3,4,5-trimethoxybenzaldehyde with 2,4-dichlorophenylhydrazine. Newly synthesized hydrazones were tested against eight Candida spp. strains in a dose response assay to determine the minimum inhibitory concentration (MIC99). Five compounds were identified as promising antifungal agents against Candida spp. (C. albicans SC5314, C. glabrata, C. tropicalis, C. parapsilosis and C. glabrata (R azoles)), with MIC99 values ranging from 16 to 32 µg/mL and selective antifungal activity over cytotoxicity.


Assuntos
Antifúngicos/farmacologia , Azóis/farmacologia , Candida/efeitos dos fármacos , Farmacorresistência Fúngica , Hidrazonas/farmacologia , Pirazóis/química , Antifúngicos/química , Candida/crescimento & desenvolvimento , Hidrazonas/química , Testes de Sensibilidade Microbiana
13.
Microbiol Spectr ; 9(2): e0095721, 2021 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-34494857

RESUMO

There is a rising global incidence of Candida strains with high levels of resistance to fluconazole and other antifungal drugs, hence the need for novel antifungal treatment strategies. Here, we describe the first evidence of antifungal activity of Q-Griffithsin (Q-GRFT), a recombinant oxidation-resistant variant of Griffithsin, a marine red algal lectin with broad-spectrum antiviral activity. We demonstrated that Q-GRFT binds to α-mannan in the Candida albicans cell wall. We also observed that Q-GRFT binding disrupted cell wall integrity and induced reactive oxidative species (ROS) formation, resulting in cell death. Furthermore, we showed that Q-GRFT inhibited the growth of other Candida species C. glabrata, C. parapsilosis, and C. krusei and had modest activity against some strains of multi- and pandrug-resistant C. auris. We found that Q-GRFT induced differential expression of numerous genes involved in response to cell stress, including those responsible for neutralizing ROS production and cell cycle regulation. In conclusion, this novel antifungal activity suggests that Q-GRFT is potentially an ideal drug candidate and represents an alternative strategy for the prevention and treatment of candidiasis. IMPORTANCE Fungal infections contribute to morbidity and mortality annually, and the number of organisms that are nonresponsive to the current available drug regimens are on the rise. There is a need to develop new agents to counter these infections and to add to the limited arsenal available to treat fungal infections. Our study has identified Q-GRFT, a broad-spectrum antiviral protein that harbors growth-inhibitory activity against several Candida strains, as a potential candidate for the prevention and treatment of fungal infections.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Candidíase/tratamento farmacológico , Lectinas de Plantas/farmacologia , Proteínas Recombinantes/farmacologia , Antivirais/farmacologia , Candida/classificação , Candidíase/microbiologia , Parede Celular/química , Parede Celular/metabolismo , Farmacorresistência Fúngica/genética , Mananas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
14.
Molecules ; 26(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34361723

RESUMO

Genito-urinary tract infections have a high incidence in the general population, being more prevalent among women than men. These diseases are usually treated with antibiotics, but very frequently, they are recurrent and lead to the creation of resistance and are associated with increased morbidity and mortality. For this reason, it is necessary to develop new compounds for their treatment. In this work, our objective is to review the characteristics of the compounds of a new formulation called Itxasol© that is prescribed as an adjuvant for the treatment of UTIs and composed of ß-arbutin, umbelliferon and n-acetyl cysteine. This formulation, based on biomimetic principles, makes Itxasol© a broad-spectrum antibiotic with bactericidal, bacteriostatic and antifungal properties that is capable of destroying the biofilm and stopping its formation. It also acts as an anti-inflammatory agent, without the adverse effects associated with the recurrent use of antibiotics that leads to renal nephrotoxicity and other side effects. All these characteristics make Itxasol© an ideal candidate for the treatment of UTIs since it behaves like an antibiotic and with better characteristics than other adjuvants, such as D-mannose and cranberry extracts.


Assuntos
Acetilcisteína/uso terapêutico , Arbutina/uso terapêutico , Produtos Biológicos/uso terapêutico , Umbeliferonas/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Acetilcisteína/química , Antibacterianos/química , Antibacterianos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Antifúngicos/química , Antifúngicos/uso terapêutico , Arbutina/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Produtos Biológicos/química , Materiais Biomiméticos/química , Materiais Biomiméticos/uso terapêutico , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Candida/patogenicidade , Combinação de Medicamentos , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Negativas/patogenicidade , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Bactérias Gram-Positivas/patogenicidade , Humanos , Masculino , Testes de Sensibilidade Microbiana , Umbeliferonas/química , Infecções Urinárias/microbiologia , Infecções Urinárias/patologia
15.
Sci Rep ; 11(1): 14099, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238976

RESUMO

There is a worldwide concern regarding the antimicrobial resistance and the inappropriate use of antifungal agents, which had led to an ever-increasing antifungal resistance. This study aimed to identify the antifungal susceptibility of colonized Candida species isolated from pediatric patients with cancer and evaluate the clinical impact of antifungal stewardship (AFS) interventions on the antifungal susceptibility of colonized Candida species. Candida species colonization was evaluated among hospitalized children with cancer in a tertiary teaching hospital, Shiraz 2017-2018. Samples were collected from the mouth, nose, urine, and stool of the patients admitted to our center and cultured on sabouraud dextrose agar. The isolated yeasts identified by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). DNA Extracted and PCR amplification was performed using the ITS1 and ITS4 primer pairs and Msp I enzyme. The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) for amphotericin B, caspofungin, and azoles. The prevalence of Candida albicans in the present study was significantly higher than other Candida species. Candida albicans species were completely susceptible to the azoles. The susceptibility rate of C. albicans to amphotericin B and caspofungin was 93.1% and 97.1%, respectively. The fluconazole MIC values of Candida albicans decreased significantly during the post-AFS period (P < 0.001; mean difference: 72.3; 95% CI of the difference: 47.36-98.62). We found that 52.5% (53/117) of the isolated C. albicans were azole-resistant before AFS implementation, while only 1.5% (2/102) of the isolates were resistant after implementation of the AFS program (P < 0.001). C. albicans fluconazole and caspofungin resistant rate also decreased significantly (P < 0.001) after implementation of the AFS program [26 (32.9%) versus 0 (0.0%) and 11 (10.9%) versus 1 (0.9%), respectively]. Besides, fluconazole use (p < 0.05) and fluconazole expenditure reduced significantly (about one thousand US$ per year) after the AFS program. Our results confirm the positive effect of optimized antifungal usage and bedside intervention on the susceptibility of Candida species after the implementation of the AFS program. C. albicans and C. glabrata exhibited a significant increase in susceptibility after the execution of the AFS program.


Assuntos
Antifúngicos/farmacologia , Gestão de Antimicrobianos , Candida/crescimento & desenvolvimento , Neoplasias/microbiologia , Adolescente , Anfotericina B/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Caspofungina/farmacologia , Criança , Pré-Escolar , Contagem de Colônia Microbiana , Suscetibilidade a Doenças , Farmacorresistência Fúngica/efeitos dos fármacos , Feminino , Fluconazol/farmacologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Triazóis/farmacologia
16.
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
17.
PLoS One ; 16(7): e0255003, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34293029

RESUMO

Fungal infections are common on oral mucosae, but their role in other oral sites is ill defined. Over the last few decades, numerous studies have reported the presence of fungi, particularly Candida species in endodontic infections, albeit in relatively small numbers in comparison to its predominant anaerobic bacteriome. Here, we review the fungal biome of primary and secondary endodontic infections, with particular reference to the prevalence and behavior of Candida species. Meta-analysis of the available data from a total of 39 studies fitting the inclusion criteria, indicate the overall weighted mean prevalence (WMP) of fungal species in endodontic infections to be 9.11% (from a cumulative total of 2003 samples), with 9.0% in primary (n = 1341), and 9.3% in secondary infections (n = 662). Nevertheless, WMP for fungi in primary and secondary infections which were 6.3% and 7.5% for culture-based studies, increased to 12.5% and 16.0% in molecular studies, respectively. The most prevalent fungal species was Candida spp. The high heterogeneity in the reported fungal prevalence suggests the need for standardized sampling, and speciation methods. The advent of the new molecular biological analytical platforms, such as the next generation sequencing (NGS), and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF), that enables identification and quantitation of a broad spectrum of hitherto unknown organisms in endodontic infections should radically alter our understanding of the endodontic mycobiome in the future. Candida spp. appear to be co-pathogens with bacteria in approximately one in ten patients with endodontic infections. Hence, clinicians should comprehend the importance and the role of fungi in endodontic infections and be cognizant of the need to eradicate both bacteria and fungi for successful therapy.


Assuntos
Candida , Candidíase/microbiologia , Doenças da Polpa Dentária/microbiologia , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Infecções Bacterianas/microbiologia , Candida/classificação , Candida/crescimento & desenvolvimento , Candida/patogenicidade , Humanos
18.
Bioorg Med Chem ; 44: 116293, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34243044

RESUMO

Antifungal development has gained increasing attention due to its limited armamentarium and drug resistance. Drug repurposing holds great potential in antifungal discovery. In this study, we explored the antifungal activity of artemisinin and its derivatives, dihydroartemisinin, artesunate and artemether. We identified that artemisinins can inhibit the growth of Candida albicans, and can enhance the activity of three commonly used antifungals, amphotericin B, micafungin and fluconazole (FLC), on Candida albicans growth and filamentation. Artemisinins possess stronger antifungal effect with FLC than with other antifungals. Among artemisinins, artemether exhibits the most potent antifungal activity with FLC and can recover the susceptibility of FLC-resistant clinical isolates to FLC treatment. The combinatorial antifungal activity of artemether and FLC is broad-spectrum, as it can inhibit the growth of Candida auris, Candida tropicalis, Candida parapsilosis, Saccharomyces cerevisiae and Cryptococcus neoformans. Mechanistic investigation revealed that artemether might enhance azole efficacy through disrupting the function of Pdr5, leading to intracellular accumulation of FLC. This study identified artemether as a novel FLC potentiator, providing potential therapeutic insights against fungal infection and antifungal resistance.


Assuntos
Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Antifúngicos/farmacologia , Artemisininas/farmacologia , Fluconazol/farmacologia , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/crescimento & desenvolvimento , Relação Estrutura-Atividade
19.
World J Microbiol Biotechnol ; 37(8): 143, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34328568

RESUMO

Antifungal and antibacterial activities of twenty-six combinations of lactic acid bacteria, propionibacteria, acetic acid bacteria and dairy yeasts inoculated in whey and milk were investigated. Associations including acetic acid bacteria were shown to suppress growth of the opportunistic yeast Candida albicans in well-diffusion assays. The protective effect of milk fermented with the two most promising consortia was confirmed in Caco-2 cell culture infected with C. albicans. Indeed, these fermented milks, after heat-treatment or not, suppressed lactate dehydrogenase release after 48 h while significant increase in LDH release was observed in the positive control (C. albicans alone) and with fermented milk obtained using commercial yogurt starter cultures. The analysis of volatile compounds in the cell-free supernatant using solid phase microextraction (SPME) coupled to gas chromatography-mass spectrometry (GC-MS) showed accumulation of significant amount of acetic acid by the consortium composed of Lactobacillus delbrueckii 5, Lactobacillus gallinarum 1, Lentilactobacillus parabuchneri 3, Lacticaseibacillus paracasei 33-4, Acetobacter syzygii 2 and Kluyveromyces marxianus 19, which corresponded to the zone of partial inhibition of C. albicans growth during well-diffusion assays. Interestingly, another part of anti-Candida activity, yielding small and transparent inhibition zones, was linked with the consortium cell fraction. This study showed a correlation between anti-Candida activity and the presence of acetic acid bacteria in dairy associations as well as a significant effect of two dairy associations against C. albicans in a Caco-2 cell model. These two associations may be promising consortia for developing functional dairy products with antagonistic action against candidiasis agents.


Assuntos
Candida/crescimento & desenvolvimento , Produtos Fermentados do Leite/microbiologia , Lactobacillales/metabolismo , Leite/microbiologia , Animais , Antibiose , Células CACO-2 , Bovinos , Produtos Fermentados do Leite/análise , Fermentação , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Lactobacillales/química , Lactobacillales/classificação , Leite/química
20.
Nat Microbiol ; 6(7): 842-851, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34083769

RESUMO

The emergent fungal pathogen Candida auris exhibits high resistance to antifungal drugs and environmental stresses, impeding treatment and decontamination1-3. The fungal factors mediating this stress tolerance are largely unknown. In the present study, we performed piggyBac, transposon-mediated, genome-wide mutagenesis and genetic screening in C. auris, and identified a mutant that grew constitutively in the filamentous form. Mapping the transposon insertion site revealed the disruption of a long non-coding RNA, named DINOR for DNA damage-inducible non-coding RNA. Deletion of DINOR caused DNA damage and an upregulation of genes involved in morphogenesis, DNA damage and DNA replication. The DNA checkpoint kinase Rad53 was hyperphosphorylated in dinorΔ mutants, and deletion of RAD53 abolished DNA damage-induced filamentation. DNA-alkylating agents, which cause similar filamentous growth, induced DINOR expression, suggesting a role for DINOR in maintaining genome integrity. Upregulation of DINOR also occurred during exposure to the antifungal drugs caspofungin and amphotericin B, macrophages, H2O2 and sodium dodecylsulfate, indicating that DINOR orchestrates multiple stress responses. Consistently, dinorΔ mutants displayed increased sensitivity to these stresses and were attenuated for virulence in mice. Moreover, genome-wide genetic interaction studies revealed links between the function of DINOR and TOR signalling, an evolutionarily conserved pathway that regulates the stress response. Identification of the mechanism(s) by which DINOR regulates stress responses in C. auris may provide future opportunities for the development of therapeutics.


Assuntos
Candida/patogenicidade , RNA Fúngico/metabolismo , RNA Longo não Codificante/metabolismo , Fatores de Virulência/metabolismo , Animais , Antifúngicos/farmacologia , Candida/genética , Candida/crescimento & desenvolvimento , Candidíase/microbiologia , Quinase do Ponto de Checagem 2/genética , Quinase do Ponto de Checagem 2/metabolismo , Dano ao DNA , Replicação do DNA , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação da Expressão Gênica , Peróxido de Hidrogênio/farmacologia , Camundongos , Morfogênese , Mutação , Fosforilação , RNA Fúngico/genética , RNA Longo não Codificante/genética , Virulência , Fatores de Virulência/genética
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