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1.
PLoS One ; 16(12): e0261755, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34941952

RESUMO

Medicinal plants represent a great source of antimicrobial and phytochemical constituents which are increasingly used to treat microbial infections and other ailments such as tuberculosis, anemia, and trachoma. Despite the use of antibiotics, antimicrobial resistance continues to be a world issue, in as much as nutrition. This study investigated the presence of phytochemicals, proximate compositions, and antimicrobial activity of methanolic extract of Carapa procera bark. The bark of Carapa procera was collected, cleaned and air dried for 72 h. The powder obtained was treated with diethyl ether and soaked in methanol (99%) for 72 h to obtain crude extract. The extract was used to test for the presence of phytochemicals and antimicrobial activities. The raw bark was used for proximate analysis. The result showed presence of steroids, tannins and saponins, but no alkaloids present. The 100 mg/mL extract had the highest inhibition zone on all tested organisms from 24.00 ± 0.94 to 26.67 ± 1.18, and 50 mg/mL showed the least (16.67 ± 1.24) on Candida albicans. Staphylococcus aureus showed the lowest minimum inhibition concentration (MIC) of 3.12 mg/mL, whereas the Gram-negative bacteria exhibited variations in their sensitivity with E. coli having the highest MIC of 25 mg/mL. The extract had high MIC (6.25 mg/mL) on Candida albicans than clotrimazole (50 mg/mL). The proximate compositions of Carapa procera were moisture (6.07 ± 0.07%), ash (12.46 ± 0.46%), crude protein (9.54 ± 0.12%), crude fat (1.42 ± 0.06%) and carbohydrate (70.50 ± 0.35%). The energy value was 1413.17 kj. Thus, Carapa procera possesses both antimicrobial and nutritional potentials worth exploring and domesticating for sustainable management and conservation.


Assuntos
Anti-Infecciosos , Candida albicans/crescimento & desenvolvimento , Meliaceae/química , Compostos Fitoquímicos , Casca de Planta/química , Staphylococcus aureus/crescimento & desenvolvimento , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia
2.
ScientificWorldJournal ; 2021: 8856147, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594161

RESUMO

Candida albicans and Candida tropicalis are the leading causes of human fungal infections worldwide. There is an increase in resistance of Candida pathogens to existing antifungal drugs leading to a need to find new sources of antifungal agents. Tormentic acid has been isolated from different plants including Callistemon citrinus and has been found to possess antimicrobial properties, including antifungal activity. The study aimed to determine the effects of tormentic and extracts from C. citrinus on C. albicans and C. tropicalis and a possible mode of action. The extracts and tormentic acid were screened for antifungal activity using the broth microdilution method. The growth of both species was inhibited by the extracts, and C. albicans was more susceptible to the extract compared to C. tropicalis. The growth of C. albicans was inhibited by 80% at 100 µg/ml of both the DCM: methanol extract and the ethanol: water extract. Tormentic acid reduced the growth of C. albicans by 72% at 100 µg/ml. The effects of the extracts and tormentic acid on ergosterol content in C. albicans were determined using a UV/Vis scanning spectrophotometer. At concentrations of tormentic acid of 25 µg/ml, 50 µg/ml, 100 µg/ml, and 200 µg/ml, the content of ergosterol was decreased by 22%, 36%, 48%, and 78%, respectively. Similarly, the DCM: methanol extract at 100 µg/ml and 200 µg/ml decreased the content by 78% and 88%, respectively. A dose-dependent decrease in ergosterol content was observed in cells exposed to miconazole with a 25 µg/ml concentration causing a 100% decrease in ergosterol content. Therefore, tormentic acid inhibits the synthesis of ergosterol in C. albicans. Modifications of the structure of tormentic acid to increase its antifungal potency may be explored in further studies.


Assuntos
Candida albicans/efeitos dos fármacos , Candida tropicalis/efeitos dos fármacos , Ergosterol/biossíntese , Melaleuca/química , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , Antifúngicos/farmacologia , Candida albicans/crescimento & desenvolvimento , Candida albicans/metabolismo , Candida tropicalis/crescimento & desenvolvimento , Candida tropicalis/metabolismo , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , Especificidade da Espécie , Espectrofotometria Ultravioleta
3.
Molecules ; 26(19)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34641314

RESUMO

The recent emergence of Zika virus (ZIKV) in Brazil and the increasing resistance developed by pathogenic bacteria to nearly all existing antibiotics should be taken as a wakeup call for the international authority as this represents a risk for global public health. The lack of antiviral drugs and effective antibiotics on the market triggers the need to search for safe therapeutics from medicinal plants to fight viral and microbial infections. In the present study, we investigated whether a mangrove plant, Bruguiera gymnorhiza (L.) Lam. (B. gymnorhiza) collected in Mauritius, possesses antimicrobial and antibiotic potentiating abilities and exerts anti-ZIKV activity at non-cytotoxic doses. Microorganisms Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 70603, methicillin-resistant Staphylococcus aureus ATCC 43300 (MRSA), Salmonella enteritidis ATCC 13076, Sarcina lutea ATCC 9341, Proteus mirabilis ATCC 25933, Bacillus cereus ATCC 11778 and Candida albicans ATCC 26555 were used to evaluate the antimicrobial properties. Ciprofloxacin, chloramphenicol and streptomycin antibiotics were used for assessing antibiotic potentiating activity. ZIKVMC-MR766NIID (ZIKVGFP) was used for assessing anti-ZIKV activity. In silico docking (Autodock 4) and ADME (SwissADME) analyses were performed on collected data. Antimicrobial results revealed that Bruguiera twig ethyl acetate (BTE) was the most potent extract inhibiting the growth of all nine microbes tested, with minimum inhibitory concentrations ranging from 0.19-0.39 mg/mL. BTE showed partial synergy effects against MRSA and Pseudomonas aeruginosa when applied in combination with streptomycin and ciprofloxacin, respectively. By using a recombinant ZIKV-expressing reporter GFP protein, we identified both Bruguiera root aqueous and Bruguiera fruit aqueous extracts as potent inhibitors of ZIKV infection in human epithelial A549 cells. The mechanisms by which such extracts prevented ZIKV infection are linked to the inability of the virus to bind to the host cell surface. In silico docking showed that ZIKV E protein, which is involved in cell receptor binding, could be a target for cryptochlorogenic acid, a chemical compound identified in B. gymnorhiza. From ADME results, cryptochlorogenic acid is predicted to be not orally bioavailable because it is too polar. Scientific data collected in this present work can open a new avenue for the development of potential inhibitors from B. gymnorhiza to fight ZIKV and microbial infections in the future.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antivirais/farmacologia , Extratos Vegetais/farmacologia , Rhizophoraceae/química , Zika virus/crescimento & desenvolvimento , Antibacterianos/química , Antifúngicos/química , Antivirais/química , Brasil , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Simulação por Computador , Sinergismo Farmacológico , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/crescimento & desenvolvimento , Maurício , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Extratos Vegetais/química , Proteus mirabilis/efeitos dos fármacos , Proteus mirabilis/crescimento & desenvolvimento , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Zika virus/efeitos dos fármacos
4.
Molecules ; 26(19)2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34641359

RESUMO

The increasing incidence of antifungal resistance represents a great challenge in the medical area and, for this reason, new therapeutic alternatives for the treatment of fungal infections are urgently required. Cold atmospheric plasma (CAP) has been proposed as a promising alternative technique for the treatment of superficial candidiasis, with inhibitory effect both in vitro and in vivo. However, little is known on the association of CAP with conventional antifungals. The aim of this study was to evaluate the effects of the association between CAP and conventional polyene antifungals on Candida albicans biofilms. C. albicans SC 5314 and a clinical isolate were used to grow 24 or 48 h biofilms, under standardized conditions. After that, the biofilms were exposed to nystatin, amphotericin B and CAP, separately or in combination. Different concentrations of the antifungals and sequences of treatment were evaluated to establish the most effective protocol. Biofilms viability after the treatments was compared to negative control. Data were compared by One-way ANOVA and post hoc Tukey (5%). The results demonstrate that 5 min exposure to CAP showed more effective antifungal effect on biofilms when compared to nystatin and amphotericin B. Additionally, it was detected that CAP showed similar (but smaller in magnitude) effects when applied in association with nystatin and amphotericin B at 40 µg/mL and 60 µg/mL. Therefore, it can be concluded that the application of CAP alone was more effective against C. albicans biofilms than in combination with conventional polyene antifungal agents.


Assuntos
Anfotericina B/farmacologia , Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Sinergismo Farmacológico , Nistatina/farmacologia , Gases em Plasma/farmacologia , Biofilmes/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento
5.
Molecules ; 26(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34361728

RESUMO

Glycyrrhetinic acid (GA) is one of many interesting pentacyclic triterpenoids showing significant anticancer activity by triggering apoptosis in tumor cell lines. This study deals with the design and synthesis of new glycyrrhetinic acid (GA)-amino acid peptides and peptide ester derivatives. The structures of the new derivatives were established through various spectral and microanalytical data. The novel compounds were screened for their in vitro cytotoxic activity. The evaluation results showed that the new peptides produced promising cytotoxic activity against the human breast MCF-7 cancer cell line while comparing to doxorubicin. On the other hand, only compounds 3, 5, and 7 produced potent activity against human colon HCT-116 cancer cell line. The human liver cancer (HepG-2) cell line represented a higher sensitivity to peptide 7 (IC50; 3.30 µg/mL), while it appeared insensitive to the rest of the tested peptides. Furthermore, compounds 1, 3, and 5 exhibited a promising safety profile against human normal skin fibroblasts cell line BJ-1. In order to investigate the mode of action, compound 5 was selected as a representative example to study its in vitro effect against the apoptotic parameters and Bax/BCL-2/p53/caspase-7/caspase-3/tubulin, and DNA fragmentation to investigate beta (TUBb). Additionally, all the new analogues were subjected to antimicrobial assay against a panel of Gram-positive and Gram-negative bacteria and the yeast candida Albicans. All the tested GA analogues 1-8 exhibited more antibacterial effect against Micrococcus Luteus than gentamicin, but they exhibited moderate antimicrobial activity against the tested bacterial and yeast strains. Molecular docking studies were also simulated for compound 5 to give better rationalization and put insight to the features of its structure.


Assuntos
Antibacterianos/síntese química , Antifúngicos/síntese química , Antineoplásicos/síntese química , Citotoxinas/síntese química , Ácido Glicirretínico/química , Peptídeos/química , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Caspase 3/química , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citotoxinas/farmacologia , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ácido Glicirretínico/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Células HCT116 , Células Hep G2 , Humanos , Células MCF-7 , Testes de Sensibilidade Microbiana , Peptídeos/farmacologia , Conformação Proteica , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
6.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361759

RESUMO

Croton ferrugineus Kunth is an endemic species of Ecuador used in traditional medicine both for wound healing and as an antiseptic. In this study, fresh Croton ferrugineus leaves were collected and subjected to hydrodistillation for extraction of the essential oil. The chemical composition of the essential oil was determined by gas chromatography equipped with a flame ionization detector and gas chromatography coupled to a mass spectrometer using a non-polar and a polar chromatographic column. The antibacterial activity was assayed against three Gram-positive bacteria, one Gram-negative bacterium and one dermatophyte fungus. The radical scavenging properties of the essential oil was evaluated by means of DPPH and ABTS assays. The chemical analysis allowed us to identify thirty-five compounds representing more than 99.95% of the total composition. Aliphatic sesquiterpene hydrocarbon trans-caryophyllene was the main constituent with 20.47 ± 1.25%. Other main compounds were myrcene (11.47 ± 1.56%), ß-phellandrene (10.55 ± 0.02%), germacrene D (7.60 ± 0.60%), and α-humulene (5.49 ± 0.38%). The essential oil from Croton ferrugineus presented moderate activity against Candida albicans (ATCC 10231) with an MIC of 1000 µg/mL, a scavenging capacity SC50 of 901 ± 20 µg/mL with the ABTS method, and very strong antiglucosidase activity with an IC50 of 146 ± 20 µg/mL.


Assuntos
Anti-Infecciosos/química , Antioxidantes/química , Croton/química , Inibidores Enzimáticos/química , Óleos Voláteis/química , Folhas de Planta/química , Monoterpenos Acíclicos/química , Monoterpenos Acíclicos/isolamento & purificação , Alcenos/química , Alcenos/isolamento & purificação , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Benzotiazóis/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Monoterpenos Cicloexânicos/química , Monoterpenos Cicloexânicos/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Sesquiterpenos Monocíclicos/química , Sesquiterpenos Monocíclicos/isolamento & purificação , Picratos/antagonistas & inibidores , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/isolamento & purificação , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação , Ácidos Sulfônicos/antagonistas & inibidores , alfa-Glucosidases/química
7.
PLoS Pathog ; 17(8): e1009861, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34398936

RESUMO

Microbial pathogens grow in a wide range of different morphologies that provide distinct advantages for virulence. In the fungal pathogen Candida albicans, adenylyl cyclase (Cyr1) is thought to be a master regulator of the switch to invasive hyphal morphogenesis and biofilm formation. However, faster growing cyr1Δ/Δ pseudorevertant (PR) mutants were identified that form hyphae in the absence of cAMP. Isolation of additional PR mutants revealed that their improved growth was due to loss of one copy of BCY1, the negative regulatory subunit of protein kinase A (PKA) from the left arm of chromosome 2. Furthermore, hyphal morphogenesis was improved in some of PR mutants by multigenic haploinsufficiency resulting from loss of large regions of the left arm of chromosome 2, including global transcriptional regulators. Interestingly, hyphal-associated genes were also induced in a manner that was independent of cAMP. This indicates that basal protein kinase A activity is an important prerequisite to induce hyphae, but activation of adenylyl cyclase is not needed. Instead, phosphoproteomic analysis indicated that the Cdc28 cyclin-dependent kinase and the casein kinase 1 family member Yck2 play key roles in promoting polarized growth. In addition, integrating transcriptomic and proteomic data reveals hyphal stimuli induce increased production of key transcription factors that contribute to polarized morphogenesis.


Assuntos
Candida albicans/crescimento & desenvolvimento , AMP Cíclico/metabolismo , Proteínas Fúngicas/metabolismo , Hifas/crescimento & desenvolvimento , Morfogênese , Proteoma/análise , Transcriptoma , Adenilil Ciclases/metabolismo , Candida albicans/genética , Candida albicans/metabolismo , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Genoma Fúngico , Hifas/genética , Hifas/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo
8.
World J Microbiol Biotechnol ; 37(8): 129, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34232401

RESUMO

Lichens are symbiotic organisms formed by a fungus and one or more photosynthetic partners which are usually alga or cyanobacterium. Their diverse and scarcely studied metabolites facilitate adaptability to extreme living conditions. We investigated Evernia prunastri (L.) Ach., a widely distributed lichen, for its antimicrobial and antioxidant potential. E. prunastri was sequentially extracted by hexane (Hex), dichloromethane (DCM) and acetonitrile (ACN) that were screened for their antioxidant and antimicrobial (against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans) activities. The Hex extract possessed the highest antioxidant capacity (87 mg ascorbic acid/g extract) corresponding to the highest content of phenols (73 mg gallic acid/g extract). The DCM and Hex extracts were both active against S. aureus (MICs of 4 and 21 µg/ml, respectively) but were less active against Gram-negative bacteria and yeast. The ACN extract exhibited activity on both S. aureus (MIC 14 µg/ml) and C. albicans (MIC 38 µg/ml) and was therefore further fractionated by silica gel column chromatography. The active compound of the most potent fraction was subsequently characterized by 1H and 13C-NMR spectroscopy and identified as evernic acid. Structural similarity analyses were performed between compounds from E. prunastri and known antibiotics from different classes. The structural similarity was not present. Antioxidant and antimicrobial activities of E. prunastri extracts originate from multiple chemical compounds; besides usnic acid, most notably evernic acid and derivatives thereof. Evernic acid and its derivatives represent possible candidates for a new class of antibiotics.


Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Parmeliaceae/química , Extratos Vegetais/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
9.
Int J Mol Sci ; 22(14)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34299220

RESUMO

Phthalides are bioactive compounds that naturally occur in the family Apiaceae. Considering their potentially versatile applications, it is desirable to determine their physical properties, activity and metabolic pathways. This study aimed to examine the utility of whole-cell biocatalysts for obtaining 3-butyl-3-hydroxyphthalide, which is the metabolite formulated during mammalian metabolism of 3-n-butylidenephthalide. We performed transformations using 10 strains of fungi, five of which efficiently produced 3-butyl-3-hydroxyphthalide. The product yield, determined by high-performance liquid chromatography, reached 97.6% when Aspergillus candidus AM 386 was used as the biocatalyst. Increasing the scale of the process resulted in isolation yields of 29-45% after purification via reversed-phase thin layer chromatography, depending on the strain of the microorganism used. We proposed different mechanisms for product formation; however, hydration of 3-n-butylidenephthalide seems to be the most probable. Additionally, all phthalides were tested against clinical strains of Candida albicans using the microdilution method. Two phthalides showed a minimum inhibitory concentration, required to inhibit the growth of 50% of organisms, below 50 µg/mL. The 3-n-butylidenephthalide metabolite was generally inactive, and this feature in combination with its low lipophilicity suggests its involvement in the detoxification pathway. The log P value of tested compounds was in the range of 2.09-3.38.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Fungos/efeitos dos fármacos , Lipídeos/química , Anidridos Ftálicos/farmacologia , Animais , Antifúngicos/química , Candida albicans/crescimento & desenvolvimento , Fungos/crescimento & desenvolvimento , Interações Hidrofóbicas e Hidrofílicas , Mamíferos , Anidridos Ftálicos/química
10.
Molecules ; 26(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299584

RESUMO

Currently, the potential utilization of fruits and vegetable waste as a source of micronutrients and antioxidants has increased. The present study, therefore, aimed to determine the antimicrobial and anti-inflammatory activities of Citrus nobilis peel extract. A modified solvent evaporation technique was employed for peel extract preparation. For effective utilization of the natural product, quantitative analysis of phenolic compounds was carried out using liquid chromatography and mass spectroscopy technique. Phenolic and flavonoids were present in high amounts, while ß-carotene and lycopene were present in vestigial amounts. The antimicrobial efficiency of peel extract was evaluated against four bacterial strains including Staphylococcus aureus (MTCC 3160), Klebsiella pneumoniae (MTCC 3384), Pseudomonas aeruginosa (MTCC 2295), and Salmonella typhimurium (MTCC 1254), and one fungal strain Candida albicans (MTCC 183), and zone of inhibition was comparable to the positive control streptomycin and amphotericin B, respectively. The extract of Citrus nobilis peels showed effective anti-inflammatory activity during human red blood cell membrane stabilization (HRBC) and albumin denaturation assay. The extracts also exhibited 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity ranging from 53.46 to 81.13%. Therefore, the obtained results suggest that Citrus nobilis peel could be used as an excellent source of polyphenols and transformed into value-added products.


Assuntos
Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Bactérias/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Citrus/química , Membrana Eritrocítica/metabolismo , Frutas/química , Metanol/química , Extratos Vegetais/farmacologia , Anti-Infecciosos/química , Anti-Inflamatórios/química , Antioxidantes/química , Humanos , Extratos Vegetais/química
11.
Molecules ; 26(14)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34299656

RESUMO

Chemical composition, antioxidant capacity, and antimicrobial activity of lavender essential oils (LEOs) extracted from three different varieties of Lavandula angustifolia Mill. (1-Moldoveanca 4, 2-Vis magic 10, and 3-Alba 7) have been determined. These plants previously patented in the Republic of Moldova were cultivated in an organic agriculture system in the northeastern part of Romania and then harvested in 3 consecutive years (2017-2019) to obtain the essential oils. From the inflorescences in the complete flowering stage, the LEOs were extracted by hydrodistillation. Then, their composition was analyzed by gas chromatography coupled with mass spectrometry (GC-MS) and by Fourier Transformed Infrared spectroscopy (FT-IR). The major identified constituents are as follows: linalool (1: 32.19-46.83%; 2: 29.93-30.97%; 3: 31.97-33.77%), linalyl acetate (1: 17.70-35.18%; 2: 27.55-37.13%; 3: 28.03-35.32%), and terpinen-4-ol (1: 3.63-7.70%; 2: 3.06-7.16%; 3: 3.10-6.53%). The antioxidant capacity as determined by ABTS and DPPH assays indicates inhibition, with the highest activity obtained for LEO var. Alba 7 from 2019. The in vitro antimicrobial activities of the LEOs and combinations were investigated as well, by using the disk diffusion method and minimum inhibitory concentration (MIC) against the Gram-positive bacterial strain Staphylococcus aureus (ATCC 6538), Gram-negative Pseudomonas aeruginosa (ATCC 27858), Escherichia coli (ATCC 25922), the yeast Candida albicans (ATCC 10231), and clinical isolates. Our results have shown that LEOs obtained from the three studied varieties of L. angustifolia manifest significant bactericidal effects against tested microorganisms (Staphylococcus aureus and Escherichia coli), and antifungal effects against Candida albicans. The mixture of LEOs (Var. Alba 7) and geranium, respectively, in tea tree EOs, in different ratios, showed a significant enhancement of the antibacterial effect against all the studied strains, except Pseudomonas aeruginosa.


Assuntos
Anti-Infecciosos , Antioxidantes , Bactérias/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Lavandula/química , Óleos Voláteis , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia
12.
Int J Mol Sci ; 22(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34065861

RESUMO

Various peptides and their derivatives have been reported to exhibit antimicrobial activities. Although these activities have been examined against microorganisms, novel methods have recently emerged for conjugation of the biomaterials to improve their activities. Here, we prepared CKR12-PLGA, in which CKR12 (a mutated fragment of human cathelicidin peptide, LL-37) was conjugated with poly (lactic-co-glycolic) acid (PLGA), and compared the antimicrobial and antifungal activities of the conjugated peptide with those of FK13 (a small fragment of LL-37) and CKR12 alone. The prepared CKR12-PLGA was characterized by dynamic light scattering and measurement of the zeta potential, critical micellar concentration, and antimicrobial activities of the fragments and conjugate. Although CKR12 showed higher antibacterial activities than FK13 against Staphylococcus aureus and Escherichia coli, the antifungal activity of CKR12 was lower than that of FK13. CKR12-PLGA showed higher antibacterial activities against S. aureus and E. coli and higher antifungal activity against Candida albicans compared to those of FK13. Additionally, CKR12-PLGA showed no hemolytic activity in erythrocytes, and scanning and transmission electron microscopy suggested that CKR12-PLGA killed and disrupted the surface structure of microbial cells. Conjugation of antimicrobial peptide fragment analogues was a successful approach for obtaining increased microbial activity with minimized cytotoxicity.


Assuntos
Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Anti-Infecciosos/química , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/genética , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candida albicans/ultraestrutura , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/ultraestrutura , Humanos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Microscopia Eletrônica de Transmissão , Mutação , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/ultraestrutura
13.
Sci Rep ; 11(1): 11610, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078983

RESUMO

Following access into the cell, colloidal silver nanoparticles exhibit generalized cytotoxic properties, thus appear as omnipotent microbicidal, but not suitable for systemic use unless are free of toxic effects on host cells. The AgNP-Serum-18 when prepared from silver nitrate, using dextrose as reducing and group-matched homologous serum as a stabilizing agent, selective endocytosis, and oxidative stress-dependent bio-functional damages to the host are mostly eliminated. For their bio-mimicking outer coat, there is the least possibility of internalization into host cells or liberation of excess oxidants in circulation following interaction with erythrocytes or vascular endothelial cells. The presence of infection-specific antibodies in the serum can make such nano-conjugates more selective. A potent antimicrobial action and a wide margin of safety for mammalian cells in comparison with very similar PVA-capped silver nanoparticles have been demonstrated by the in-vitro challenge of such nanoparticles on different microbes, human liver cell-line, and in-vivo study on mice model. This may open up wide-range therapeutic prospects of colloidal nanoparticles.


Assuntos
Antibacterianos/farmacologia , Nanopartículas Metálicas/química , Nitrato de Prata/farmacologia , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Antibacterianos/síntese química , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Coloides , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Nanopartículas Metálicas/ultraestrutura , Camundongos , Testes de Sensibilidade Microbiana , Especificidade de Órgãos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
14.
Microbiol Res ; 250: 126806, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34157481

RESUMO

New strategies that enable fast and accurate visualization of Candida biofilms are necessary to better study their structure and response to antifungals agents. Here, we applied whole slide imaging (WSI) to study biofilm formation of Candida species. Three relevant biofilm-forming Candida species (C. albicans ATCC 10231, C. glabrata ATCC 2001, and C. tropicalis ATCC 750) were cultivated on glass coverslips both in presence and absence of widely used antifungals. Accumulated biofilms were stained with fluorescent markers and scanned in both bright-field and fluorescence modes using a WSI digital scanner. WSI enabled clear assessment of both size and structural features of Candida biofilms. Quantitative analyses readily detected reductions in biofilm-covered surface area upon antifungal exposure. Furthermore, we show that the overall biofilm growth can be adequately assessed across both bright-field and fluorescence modes. At the single-cell level, WSI proved adequate, as morphometric parameters evaluated with WSI did not differ significantly from those obtained with scanning electron microscopy, considered as golden standard at single-cell resolution. Thus, WSI allows for reliable visualization of Candida biofilms enabling both large-scale growth assessment and morphometric characterization of single-cell features, making it an important addition to the available microscopic toolset to image and analyse fungal biofilm growth.


Assuntos
Biofilmes/crescimento & desenvolvimento , Candida/fisiologia , Ensaios de Triagem em Larga Escala/métodos , Microscopia Eletrônica de Varredura/métodos , Imagem Óptica/métodos , Candida/classificação , Candida/crescimento & desenvolvimento , Candida/ultraestrutura , Candida albicans/crescimento & desenvolvimento , Candida albicans/ultraestrutura , Candida glabrata/crescimento & desenvolvimento , Candida glabrata/ultraestrutura , Candida tropicalis/crescimento & desenvolvimento , Candida tropicalis/ultraestrutura
15.
Int J Nanomedicine ; 16: 3091-3103, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33953557

RESUMO

Objective: To synthesize and determine the antifungal activity of AgBr-nanoparticles (NP) @CTMAB (cetyltrimethyl-ammonium bromide) against Candida albicans (C. albicans) for use in the field of denture cleaning. Methods: The morphology and structure of AgBr-NP@CTMAB were characterized by IR, UV-Vis, XRD and SEM. The antifungal potential of AgBr-NP@CTMAB against C. albicans was determined by colony formation assay and growth curve analysis. PMMA containing AgBr-NP@CTMAB was prepared, and the long-term antifungal efficacy was analyzed. The effect against C. albicans biofilm was analyzed by SEM and OD600 , and the color changes of the specimens were observed by stereomicroscopy after 1 week of incubation. Cytotoxicity to human oral gingival fibroblasts and oral mucosal epithelial cells was detected by Cell Counting Kit-8 (CCK-8) in vitro. Results: The compound showed a good crystalline phase, the presence of AgBr nanoparticles and the hybridization of CTMAB+ with AgBr-NPs. AgBr-NP@CTMAB showed significant antifungal activity against C. albicans at concentrations of 10 µg/mL and 20 µg/mL. PMMA specimens containing AgBr-NP@CTMAB showed no long-term antifungal effect against C. albicans biofilm. The clearance rate of C. albicans attached to PMMA was 44.73% after soaking in 10 µg/mL AgBr-NP@CTMAB solution for 30 min and 91.35% for 8 h. There was no significant residual cytotoxicity or visual color change after soaking. Significance: AgBr-NP@CTMAB showed promising potential treatment for denture cleaners.


Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Cetrimônio/química , Nanopartículas/química , Polimetil Metacrilato/química , Antifúngicos/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candida albicans/fisiologia , Técnicas de Química Sintética , Humanos , Nanotecnologia
16.
mSphere ; 6(3)2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952658

RESUMO

Candida albicans is a major human fungal pathogen that encounters varied host environments during infection. In response to environmental cues, C. albicans switches between ovoid yeast and elongated hyphal growth forms, and this morphological plasticity contributes to virulence. Environmental changes that alter the cell's metabolic state could be sensed by sirtuins, which are NAD+-dependent deacetylases. Here, we studied the roles of three sirtuin deacetylases-Sir2, Hst1, and Hst2-in the hyphal growth of C. albicans We made single, double, and triple sirtuin knockout strains and tested their ability to switch from yeast to hyphae. We found that true hypha formation was significantly reduced by the deletion of SIR2 but not HST1 or HST2 Moreover, the expression of hypha-specific genes HWP1, ALS3, and ECE1 decreased in the sir2Δ/Δ mutant compared to the wild type. This regulation of hypha formation was likely dependent on the deacetylase activity of Sir2, as a similar defect in hypha formation was observed when an asparagine known to be required for deacetylation was mutated. Finally, we found that Sir2 and Hst1 were localized to the nucleus, with Sir2 specifically focused in the nucleolus. This nuclear localization suggests a role for Sir2 and Hst1 in regulating gene expression. In contrast, Hst2 was localized to the cytoplasm. In conclusion, our results suggest that Sir2 plays a critical and nonredundant role in hyphal growth of C. albicans IMPORTANCE Candida albicans is one of the most common causes of hospital-acquired systemic fungal infections in the United States. It can switch between ovoid yeast and elongated hyphal growth forms in response to environmental cues. This morphological transition is essential for its survival in the host. Thus, identifying regulators involved in this process can lead to new therapies. In this study, we examined the contribution of three regulators called sirtuins (Sir2, Hst1, and Hst2) to the yeast-to-hypha transition of C. albicans We found that loss of Sir2 but not Hst1 or Hst2 hampered hypha formation. Moreover, the defect was caused by the loss of the catalytic activity of Sir2. Our study may lay the groundwork for discovering novel targets for antifungal therapies.


Assuntos
Candida albicans/crescimento & desenvolvimento , Candida albicans/genética , Regulação Fúngica da Expressão Gênica/genética , Hifas/crescimento & desenvolvimento , Sirtuínas/genética , Candida albicans/enzimologia , Nucléolo Celular , Hifas/genética , Sirtuína 2/genética , Sirtuína 2/metabolismo , Sirtuínas/classificação , Sirtuínas/metabolismo
17.
Nat Commun ; 12(1): 2560, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33963193

RESUMO

The commensal fungus Candida albicans often causes life-threatening infections in patients who are immunocompromised with high mortality. A prominent but poorly understood risk factor for the C. albicans commensal‒pathogen transition is the use of broad-spectrum antibiotics. Here, we report that ß-lactam antibiotics cause bacteria to release significant quantities of peptidoglycan fragments that potently induce the invasive hyphal growth of C. albicans. We identify several active peptidoglycan subunits, including tracheal cytotoxin, a molecule produced by many Gram-negative bacteria, and fragments purified from the cell wall of Gram-positive Staphylococcus aureus. Feeding mice with ß-lactam antibiotics causes a peptidoglycan storm that transforms the gut from a niche usually restraining C. albicans in the commensal state to promoting invasive growth, leading to systemic dissemination. Our findings reveal a mechanism underlying a significant risk factor for C. albicans infection, which could inform clinicians regarding future antibiotic selection to minimize this deadly disease incidence.


Assuntos
Candida albicans/patogenicidade , Candidíase/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Peptidoglicano/toxicidade , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , beta-Lactamas/efeitos adversos , Animais , Antibacterianos/efeitos adversos , Candida albicans/crescimento & desenvolvimento , Candidíase/complicações , Candidíase/tratamento farmacológico , Candidíase/patologia , Parede Celular/química , Parede Celular/efeitos dos fármacos , Cromatografia Líquida , Feminino , Bactérias Gram-Negativas/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/metabolismo , Humanos , Hifas/crescimento & desenvolvimento , Hifas/patogenicidade , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos BALB C , Peptidoglicano/química , Infecções Estafilocócicas/complicações , Staphylococcus aureus/química , Staphylococcus aureus/metabolismo
18.
Fungal Genet Biol ; 152: 103568, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33991663

RESUMO

Metarhizium anisopliae is an important entomopathogenic species and model for arthropod-fungus interaction studies. This fungus harbors a diverse arsenal of unexplored secondary metabolite biosynthetic gene clusters, which are suggested to perform diverse roles during host interaction and soil subsistence as a saprophytic species. Here we explored an unusual carnitine acyltransferase domain-containing highly reducing polyketide synthase found in the genome of M. anisopliae. Employing heterologous expression in Aspergillus nidulans, two new polyketides were obtained, named BAA and BAB, as well as one known polyketide [(2Z,4E,6E)-octa-2,4,6-trienedioic acid]. Intra-hemocoel injection of the most abundant compound (BAA) in the model-arthropod Galleria mellonella larvae did not induce mortality or noticeable alterations, suggesting that this compound may not harbor insecticidal activity. Also, the potential role of such molecules in polymicrobial interactions was evaluated. Determination of minimum inhibitory concentration assays using distinct fungal species revealed that BAA and BAB did not alter Cryptococcus neoformans growth, while BAA exhibited weak antifungal activity against Saccharomyces cerevisiae. Unexpectedly, these compounds increased Candida albicans growth compared to control conditions. Furthermore, BAA can mitigate the fungicidal effects of fluconazole over C. albicans. Although the exact role of these compounds on the M. anisopliae life cycle is elusive, the described results add up to the complexity of secondary metabolites produced by Metarhizium spp. Moreover, up to our knowledge, these are the first polyketides isolated from filamentous fungi that can boost the growth of another fungal species.


Assuntos
Vias Biossintéticas/genética , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Metarhizium/genética , Metarhizium/metabolismo , Policetídeos/metabolismo , Policetídeos/farmacologia , Animais , Antifúngicos , Aspergillus nidulans/genética , Fungos/efeitos dos fármacos , Regulação Fúngica da Expressão Gênica , Genoma Fúngico/genética , Larva/microbiologia , Interações Microbianas/fisiologia , Testes de Sensibilidade Microbiana , Mariposas , Família Multigênica , Policetídeos/química , Policetídeos/isolamento & purificação , Metabolismo Secundário/genética
19.
ScientificWorldJournal ; 2021: 6625216, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33994882

RESUMO

Cobalt oxide nanoparticles (CoO NPs) were synthesized by the calcination method from the Co (II) complex which has the formula [Co(PVA)(P-ABA)(H2O)3], PVA = polyvinyl alcohol, and P-ABA = para-aminobenzoic acid. The calcination temperature was 550°C, and the products were characterized by element analysis, thermal analyses (TGA and DTA), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), UV-Vis spectra, and scanning electron microscopy (SEM) techniques. The kinetic and thermodynamic parameters (∆H ∗ , ∆G ∗ , and ∆S ∗ ) for the cobalt (II) complex are calculated. The charges been carried by the atoms cause dipole moment 10.53 and 3.84 debye and total energy 11.04 × 102 and 24.80 × 102 k Cal mol-1 for the Co (II) complex and cobalt oxide, respectively. X-ray diffraction confirmed that the resulting oxide was pure single-crystalline CoO nanoparticles. Scanning electron microscopy indicating that the crystallite size of cobalt oxide nanocrystals was in the range of 36-54 nm. Finally, the antimicrobial activity of cobalt oxide nanoparticles was evaluated using four bacterial strains and one fungal strain. Two strains of Gram-positive cocci (Staphylococcus aureus and Enterococcus faecalis), two strains of Gram-negative bacilli (Escherichia coli and Pseudomonas aeruginosa), and one strain of yeast such as fungi (Candida albicans) were used in this study.


Assuntos
Ácido 4-Aminobenzoico/química , Antibacterianos/síntese química , Nanopartículas Metálicas/química , Óxidos/síntese química , Álcool de Polivinil/química , Antibacterianos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Cobalto/farmacologia , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/crescimento & desenvolvimento , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Cinética , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Óxidos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Termodinâmica
20.
Biochem Biophys Res Commun ; 561: 106-112, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34022710

RESUMO

Candida albicans is an important opportunistic fungal pathogen of immunocompromised individuals. The ability to switch between yeast and hyphal growth forms is critical for its pathogenesis. Hyphal development in C. albicans requires two temporally linked regulations for initiation and maintenance. Here, we performed transcriptome sequencing (RNA-Seq) to analyze the transcriptional consequences for the two different phases of hyphal development. Genome-wide transcription profiling reveals that the sets associated with hyphal initiation were significantly enriched in genes for hyphal cell wall, biofilm matrix and actin polarization. In addition to hypha-specific genes, numerous genes involved in iron acquisition, such as FTR1 and SEF1, are highly induced specifically during sustained hyphal development even when additional free iron is supplied in the medium. Therefore, iron uptake genes are induced by signals that can support prolonged hyphal development in an iron-independent manner. The induction of iron acquisition genes during hyphal elongation was further confirmed by quantitative reverse transcription-PCR under various hypha-inducing conditions. Remarkably, preventing C. albicans from acquiring iron blocks BRG1 activation, leading to impaired hyphal maintenance, and ectopically expressed BRG1 can sustain hyphal development bypassing the requirement of iron. Our study elucidates an underlying mechanism of how multiple virulence factors are interconnected and are induced simultaneously during infection.


Assuntos
Candida albicans/crescimento & desenvolvimento , Candida albicans/metabolismo , Proteínas Fúngicas/metabolismo , Hifas/crescimento & desenvolvimento , Ferro/metabolismo , Candida albicans/genética , Proteínas Fúngicas/genética , Hifas/genética , Hifas/metabolismo , Virulência
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