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1.
J Mycol Med ; 34(2): 101478, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582029

RESUMO

INTRODUCTION: Since the drug resistance in Candida species is becoming a serious clinical challenge, novel alternative therapeutic options, particularly herbal medicine, have attracted increasing interest. This study aimed to pinpoint the potential antifungal activity of crocin (Cro), the efficacy of the niosomal formulation of Cro (NCro), and the synergistic activity of both formulations in combination with fluconazole (FLC) against susceptible and resistant C. albicans isolates. MATERIAL AND METHODS: NCro was formulated using the heating method. The in vitro antimycotic activity of Cro, NCro, and FLC was evaluated. Checkerboard and isobologram assays evaluated the interaction between both formulations of Cro and FLC. Necrotic and apoptotic effects of different agents were analyzed using the flow cytometry method. In silico study was performed to examine the interactions between Lanosterol 14 alpha-demethylase and Cro as a part of our screening compounds with antifungal properties. RESULTS: NCro exhibited high entrapment efficiency up to 99.73 ± 0.54, and the mean size at 5.224 ± 0.618 µm (mean ± SD, n = 3). Both formulations of Cro were shown to display good anticandidal activity against isolates. The synergistic effect of the NCro in combination with FLC is comparable to Cro (P-value =0.03). Apoptotic indicators confirmed that tested compounds caused cell death in isolates. The docking study indicated that Cro has interactivity with the protein residue of 14α-demethylase. CONCLUSION: The results showed a remarkable antifungal effect by NCro combined with FLC. Natural compounds, particularly nano-sized carrier systems, can act as an effective therapeutic option for further optimizing fungal infection treatment.


Assuntos
Antifúngicos , Candida albicans , Carotenoides , Sinergismo Farmacológico , Fluconazol , Lipossomos , Testes de Sensibilidade Microbiana , Candida albicans/efeitos dos fármacos , Antifúngicos/farmacologia , Carotenoides/farmacologia , Fluconazol/farmacologia , Humanos , Simulação por Computador , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Farmacorresistência Fúngica/efeitos dos fármacos , Simulação de Acoplamento Molecular
2.
Ther Deliv ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651887

RESUMO

Despite having current advanced therapy, vulvovaginal candidiasis (VVC) remains a common yet debated healthcare-associated topic worldwide due to multi-drug resistance Candida species. In our review, we outlined and highlighted upcoming values with scope of existing and emerging information regarding the possibility of using various natural molecules combined with modern technology that shows promising anti-candida activity in VVC. Furthermore, in this review, we compiled herbal drug molecules and their nanocarriers approach for enhancing the efficacy and stability of herbal molecules. We have also summarized the patent literature available on herbal drug molecules and their nanoformulation techniques that could alternatively become a new innovative era to combat resistance VVC.


There is a type of fungi called Candida that is responsible for infections like vulvovaginal candidiasis in the human vagina. Due to resistance of currently available antifungal medicines, there are side effects on the body. Therefore, researchers are studying and preparing natural-based medicine from plants which may provide very good effects on human health. Also, herbal-based medicines have shown evidence based good antifungal activity. Combinations of herbal drugs with very small-sized particles called nanomaterials have added advantage as it helps herbs (drug) to reach their target. Its activity is enhanced as it stays for longer time in the body. So, in the future more research is needed to make sure plant medicines are safe and work well on vaginal infections and its uses should be promoted so that could be a good solution for treating vaginal candidiasis.

3.
J Pharm Bioallied Sci ; 16(Suppl 1): S265-S267, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38595550

RESUMO

Aim: This research was done to analyze the effectiveness related to herbal chemicals in tackling candidiasis. Materials and Methods: Grounded and ethanol-extracted residues of plants like Avicennia marina, Fagonia indica, Portulaca oleracea, Lawsania inermis, Ziziphus spina, Asphodelus tenuifolius, and Salvadora persica were used in the study. The extract was used against candida species, after which the antibacterial as well as cytotoxicity toward the former were evaluated. Results: L. inermis and P. oleracea with minimal inhibitory concentration of approx. 10 cenmL had an increased activity against candida species. The preparations of these plants acted against Candida albicans during its stages related to pathogenesis during biofilm production. Superadded infections like in case of bacterial infections along with candida can be difficult to cure. On human RBCs, these plant preparations had no toxicity at their minimum inhibitory concentration level. Conclusion: We concluded that, as far as being anti-candida and acting against MDR bacterial infections, preparations of plants were effective as an alternative to allopathic drugs.

4.
Antibiotics (Basel) ; 13(4)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38667023

RESUMO

An endophytic symbiont P. aeruginosa-producing anticandidal siderophore was recovered from mangrove leaves for the first time. Production was optimal in a succinate medium supplemented with 0.4% citric acid and 15 µM iron at pH 7 and 35 °C after 60 h of fermentation. UV spectra of the acidic preparation after purification with Amberlite XAD-4 resin gave a peak at 400 nm, while the neutralized form gave a peak at 360 nm. A prominent peak with RP-HPLC was obtained at RT 18.95 min, confirming its homogeneity. It was pH stable at 5.0-9.5 and thermally stable at elevated temperatures, which encourages the possibility of its application in extreme environments. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) against Candida spp. Were in the range of 128 µg/mL and lower. It enhanced the intracellular iron accumulation with 3.2-4.2-fold (as judged by atomic absorption spectrometry) with a subsequent increase in the intracellular antioxidative enzymes SOD and CAT. Furthermore, the malondialdehyde (MDA) concentration due to cellular lipid peroxidation increased to 3.8-fold and 7.3-fold in C. albicans and C. tropicalis, respectively. The scanning electron microscope (SEM) confirmed cellular damage in the form of roughness, malformation, and production of defensive exopolysaccharides and/or proteins after exposure to siderophore. In conclusion, this anticandidal siderophore may be a promising biocontrol, nonpolluting agent against waterborne pathogens and pathogens of the skin. It indirectly kills Candida spp. by ferroptosis and mediation of hyperaccumulation of iron rather than directly attacking the cell targets, which triggers the activation of antioxidative enzymes.

5.
Int J Clin Pediatr Dent ; 17(1): 26-30, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38559866

RESUMO

Purpose: The current literature proposes a probable role of Candida albicans (C. albicans) in its etiopathogenesis in early childhood caries (ECC). This study aimed to isolate C. albicans species in children with and without ECC and compare the antifungal efficacy of neem, miswak, cinnamon, clove, stevia, and ketoconazole. This study also aimed to assess and compare salivary pH in children with and without ECC. Materials and methods: A total of 60 children were included in the study, who were divided into two groups-group I (children with ECC) and group II (children without ECC). Plaque samples were collected and streaked on Sabouraud dextrose agar (SDA). C. albicans isolates were evaluated, and their susceptibility to herbal agents was tested and compared. Saliva samples were collected, and salivary pH was tested and compared. Results: The presence of C. albicans was significantly higher in group I (76.7%) as compared to group II (23.3%). The mean zone of inhibition for neem was 4.9 mm, whereas, for miswak, it was 4.5 mm; for cinnamon, 9.3 mm; for clove, 3.8 mm; for stevia, 10.9 mm; and for ketoconazole it was 21.09 mm. The mean salivary pH for group I was 6.7, and that for group II was 7.3. Conclusion: Candida albicans (C. albicans) carriage in children with ECC was significantly higher than in children without ECC. All herbal agents showed significant antifungal activity, with stevia showing the highest activity. The average salivary pH of children without ECC was slightly higher than that of children with ECC. How to cite this article: Siddaiah SB, Sinha S, BR A. Microbiological Evaluation of Herbal Extracts against Candida albicans in Early Childhood Caries Patients: An In Vitro Study. Int J Clin Pediatr Dent 2024;17(1):26-30.

6.
Technol Health Care ; 32(4): 2629-2641, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38517819

RESUMO

BACKGROUND: Denture stomatitis, frequently encountered, is generally addressed symptomatically, with limited exploration of preventive approaches involving antifungal medicinal plants. OBJECTIVE: This study assessed the impact of Artemisia sieberi extracts on the candida growth of conventional and digitally processed acrylic materials. METHOD: Thirty acrylic resin discs (3 mm thickness × 10 mm diameter) were prepared by conventional or CAD/CAM technology (milling and 3D printing). The resin discs were exposed to simulated brushing, thermocycling, and immersion in Artemisia sieberi extract for 8 hours. The surface roughness of the discs was assessed at baseline and after immersion in Artemisia sieberi extract. Candida growth was quantified through colony-forming units (CFU/mL). Data was analyzed using SPSS v.22 (α⩽ 0.05). RESULTS: Irrespective of the material type, the post-immersion surface roughness was significantly higher compared to pre-immersion values (p< 0.05). Candida growth was significantly higher in conventional acrylic materials than digitally fabricated acrylics (p< 0.05). At × 3, Ra and CFU were found to be moderately positive and non-significantly correlated (R= 0.664, p= 0.149). At × 4, Ra and CFU were found to be weak positive and non-significantly correlated (R= 0.344, p= 0.503). CONCLUSION: Artemisia sieberi extracts had a notable impact on digitally fabricated denture acrylics, reducing candida albicans growth compared to conventional heat-cured acrylic. This suggests a potential role for these extracts in improving denture hygiene and preventing denture stomatitis, particularly in the context of digitally fabricated dentures.


Assuntos
Resinas Acrílicas , Artemisia , Extratos Vegetais , Propriedades de Superfície , Artemisia/química , Resinas Acrílicas/farmacologia , Resinas Acrílicas/química , Extratos Vegetais/farmacologia , Humanos , Candida/efeitos dos fármacos , Desenho Assistido por Computador , Impressão Tridimensional , Teste de Materiais
7.
Phytother Res ; 38(5): 2518-2538, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38450815

RESUMO

Invasive candidiasis, attributed to Candida albicans, has long been a formidable threat to human health. Despite the advent of effective therapeutics in recent decades, the mortality rate in affected patient populations remains discouraging. This is exacerbated by the emergence of multidrug resistance, significantly limiting the utility of conventional antifungals. Consequently, researchers are compelled to continuously explore novel solutions. Natural phytochemicals present a potential adjunct to the existing arsenal of agents. Previous studies have substantiated the efficacy of phytochemicals against C. albicans. Emerging evidence also underscores the promising application of phytochemicals in the realm of antifungal treatment. This review systematically delineates the inhibitory activity of phytochemicals, both in monotherapy and combination therapy, against C. albicans in both in vivo and in vitro settings. Moreover, it elucidates the mechanisms underpinning the antifungal properties, encompassing (i) cell wall and plasma membrane damage, (ii) inhibition of efflux pumps, (iii) induction of mitochondrial dysfunction, and (iv) inhibition of virulence factors. Subsequently, the review introduces the substantial potential of nanotechnology and photodynamic technology in enhancing the bioavailability of phytochemicals. Lastly, it discusses current limitations and outlines future research priorities, emphasizing the need for high-quality research to comprehensively establish the clinical efficacy and safety of phytochemicals in treating fungal infections. This review aims to inspire further contemplation and recommendations for the effective integration of natural phytochemicals in the development of new medicines for patients afflicted with C. albicans.


Assuntos
Antifúngicos , Candida albicans , Compostos Fitoquímicos , Compostos Fitoquímicos/farmacologia , Candida albicans/efeitos dos fármacos , Antifúngicos/farmacologia , Humanos , Animais , Candidíase/tratamento farmacológico , Testes de Sensibilidade Microbiana
8.
Pol J Vet Sci ; 27(1): 25-33, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38511572

RESUMO

Candida albicans, a polymorphic yeast, is a physiological component of the human and animal commensal microbiome. It is an etiological factor of candidiasis, which is treated by azole antifungals. Growing resistance to azoles is a reason to look for other alternative treatment options. The pharmacotherapeutic use of plant extracts and essential oils has become increasingly important. In our experiment, C. albicans showed susceptibility to four observed plant extracts and essential oils from peppermint ( Mentha piperita), thyme ( Thymus vulgaris), sage ( Salvia officinalis), and oregano ( Origanum vulgare). Oregano plant extract and essential oil showed the highest antifungal activity, at MIC values of 4.9 mg/mL and 0.4 mg/mL respectively. Therefore, it was subjected to further research on the influence of virulence factors - biofilm formation, extracellular phospholipase production and germ tube formation. Oregano plant extract and essential oil showed an inhibitory effect on the observed C. albicans virulence factors at relatively low concentrations. The extract inhibited the adherence of cells at MIC 12.5 mg/mL and essential oil at MIC 0.25 mg/mL. Degradation of the formed biofilm was detected at MIC 14.1 mg/mL for plant extract and at MIC 0.4 mg/mL for essential oil. Extracellular phospholipase production was most effectively inhibited by the essential oil. In particular, the number of isolates with intensive extracellular phospholipase production decreased significantly. Of the 12 isolates intensively producing extracellular phospholipase, only 1 isolate (4.5%) retained intense production. Essential oil caused up to a 100 % reduction in germ tubes formation and plant extract reduced their formation depending on the concentration as follows: 2.6% (0.8 mg/mL), 21.2 % (6.25 mg/mL), and 64.5 % (12.5 mg/mL) compared to the control.


Assuntos
Óleos Voláteis , Origanum , Humanos , Animais , Óleos Voláteis/farmacologia , Candida albicans , Extratos Vegetais/farmacologia , Fatores de Virulência , Testes de Sensibilidade Microbiana/veterinária , Antifúngicos/farmacologia , Fosfolipases/farmacologia , Óleos de Plantas/farmacologia
9.
Pathogens ; 13(3)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38535596

RESUMO

Urinary tract infections occupy a special niche among diseases of infectious etiology. Many microorganisms associated with urinary tract infections, such as Klebsiella oxytoca, Enterococcus spp., Morganella morganii, Moraxella catarrhalis, Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus, Staphylococcus spp., and Candida spp., can form biofilms. The aim of this research was to study the effect of the enzyme L-lysine-Alpha-oxidase (LO) produced by the fungus Trichoderma harzianum Rifai on the biofilm formation process of microorganisms associated with urinary tract infections. Homogeneous LO showed a more pronounced effect than the culture liquid concentrate (cCL). When adding samples at the beginning of incubation, the maximum inhibition was observed in relation to Enterococcus faecalis 5960-cCL 86%, LO 95%; Enterococcus avium 1669-cCL 85%, LO 94%; Enterococcus cloacae 6392-cCL 83%, LO-98%; and Pseudomonas aeruginosa 3057-cCL 70%, LO-82%. The minimum inhibition was found in Candida spp. Scanning electron microscopy was carried out, and numerous morphological and structural changes were observed in the cells after culturing the bacterial cultures in a medium supplemented with homogeneous LO. For example, abnormal division was detected, manifesting as the appearance of joints in places where the bacteria diverge. Based on the results of this work, we can draw conclusions about the possibility of inhibiting microbial biofilm formation with the use of LO; especially significant inhibition was achieved when the enzyme was added at the beginning of incubation. Thus, LO can be a promising drug candidate for the treatment or prevention of infections associated with biofilm formation.

10.
Crit Rev Microbiol ; : 1-11, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38497208

RESUMO

INTRODUCTION: In 2022, the World Health Organization published a report encouraging researchers to focus on Candida spp. to strengthen the global response to fungal oral infections and antifungal resistance. In the context of innovative research, it seems pertinent to investigate the antifungal potential of natural extracts of plants and the methodology involved in the recent reports. The aim of this systematic review is to identify the current state of in vitro research on the evaluation of the ability of plant extracts to inhibit Candida spp. MATERIAL AND METHODS: A bibliographic search has been developed to on a 10-year period to identify which plant extracts have an antifungal effect on the Candida spp. found in the oral cavity. RESULTS: A total of 20 papers were reviewed and fulfilled all the selection criteria and were included in the full data analysis. DISCUSSION: Plants have been tested in a wide range of states - whole extracts, extraction of particular components such as flavonoids or polyphenols, or even using the plant to synthesize nanoparticles. Of forty-five plants tested, five of them did not show any effect against Candida spp., which weren't part of the same family. There is a wide range of plant that exhibit antifungal proprieties. CONCLUSION: Many plants have been tested in a wide range of states - whole extracts, extraction of components such as flavonoids or polyphenols, or even using the plant to synthetize nanoparticles. The combination of plants, the addition of plants to a traditional antifungal and the interference with adhesion provided by some plants seem to be promising strategies. Nonetheless, on contrary to drugs, there is a critical lack of standardization on methodologies and protocols, which makes it difficult to compare data and, consequently, to conclude, beyond doubts, about the most promising plants to fight Candida spp. oral infections.

11.
J Fungi (Basel) ; 10(3)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38535221

RESUMO

Candida albicans is a clinically significant opportunistic fungus that is generally treated with antifungal drugs such as itraconazole and fluconazole. However, the recent emergence of fungal resistance has made treatment increasingly difficult. Therefore, novel antifungal treatment methods are urgently required. Hexanol ethosome photodynamic therapy (HE-PDT) is a method that uses photosensitizers (PS), such as hexanol ethosome, to exert antifungal effects, and can be used to treat resistant fungal strains. However, due to the high dose of PS required for antifungal treatment, excess photosensitizers may remain. Furthermore, once exposed to light, normal tissues or cells are damaged after photodynamic therapy, which limits the clinical application of HE-PDT. Therefore, improving the efficacy without increasing the dose is the key to this treatment. In this study, the antifungal effect of copper sulfate combined with HE-PDT was investigated, and its mechanism was explored. The results suggested that exogenous copper sulfate significantly increased the antifungal effect of HE-PDT by enhancing the rate of C. albicans inhibition, increasing reactive oxygen species (ROS) accumulation, increasing the rate of apoptosis, and altering the mitochondrial membrane potential (MMP) and ATP concentration, which is related to the downregulation of apoptosis-inducing factor (AIF1) expression. In conclusion, copper sulfate combined with photodynamic therapy significantly inhibited the activity of C. albicans by inducing apoptosis. The combined approach reported herein provides new insights for future antifungal therapy.

12.
World J Microbiol Biotechnol ; 40(5): 152, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38553646

RESUMO

Saponins are a large group of compounds, produced mostly by plants as a side product of their metabolic activity. These compounds have attracted much attention over the years mostly because of their surface activity and antibacterial, anti-inflammatory and antifungal properties. On the other hand, most of the hitherto research has concerned the action of saponins against microbial cells as a whole. Therefore, knowing the possible interaction of saponins with biomembrane, we decided to check in-vitro the influence of saponin-rich extract of Saponaria officinalis on spheroplasts of two Candida sp. The obtained results show that 10 mg L- 1 of extract increased the permeability of spheroplasts up to 21.76% relative to that of the control sample. Moreover, the evaluation of surface potential has revealed a decrease by almost 10 mV relative to that of the untreated samples. Such results suggest its direct correlation to integration of saponins into the biomembrane structure. The obtained results have proved the antifungal potential of saponins and their ability of permeabilization of cells. This proves the high potential of saponins use as additives to antifungal pharmaceutics, which is expected to lead to improvement of their action or reduction of required dosage.


Assuntos
Saponaria , Saponinas , Antifúngicos/farmacologia , Antifúngicos/química , Saponaria/química , Saponinas/farmacologia , Saponinas/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Candida , Permeabilidade
13.
Phytomedicine ; 128: 155515, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38484624

RESUMO

BACKGROUND: Vulvovaginal candidiasis (VVC) is a common infection that affects the female reproductive tract. Pulsatilla decoction (PD), a traditional Chinese herbal medicine, is a classic and effective prescription for VVC. However, its mechanism of action remains unclear. PURPOSE: This study aimed to evaluate the efficacy and potential mechanism of action of the n-butanol extract of Pulsatilla decoction (BEPD) in VVC treatment. METHODS: High performance liquid chromatography (HPLC) was used to detect the main active ingredients in BEPD. A VVC-mouse model was constructed using an estrogen-dependent method to evaluate the efficacy of BEPD in VVC treatment. Fungal burden and morphology in the vaginal cavity were comprehensively assessed. Candida albicans-induced inflammation was examined in vivo and in vitro. The effects of BEPD on the Protein kinase Cδ (PKCδ) /NLR family CARD domain-containing protein 4 (NLRC4)/Interleukin-1 receptor antagonist (IL-1Ra) axis were analyzed using by immunohistochemistry (IHC), immunofluorescence (IF), western blot (WB), and reverse transcription-quantitative polymerase chain reaction (qRT-PCR). RESULTS: BEPD inhibited fungal growth in the vagina of VVC mice, preserved the integrity of the vaginal mucosa, and suppressed inflammatory responses. Most importantly, BEPD activated the "silent" PKCδ/NLRC4/IL-1Ra axis and negatively regulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, thereby exerting a therapeutic efficacy on VVC. CONCLUSIONS: BEPD effects on mice with VVC were dose-dependent. BEPD protects against VVC by inhibiting inflammatory response and NLRP3 inflammasome via the activation of the PKCδ/NLRC4/IL-1Ra axis. This study revealed the pharmacological mechanism of BEPD in VVC treatment and provided further evidence for the application of BEPD in VVC treatment.


Assuntos
Candidíase Vulvovaginal , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Pulsatilla , Animais , Feminino , Camundongos , Candida albicans/efeitos dos fármacos , Candidíase Vulvovaginal/tratamento farmacológico , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína Quinase C-delta/metabolismo , Pulsatilla/química , Vagina/microbiologia , Vagina/efeitos dos fármacos
14.
Med Mycol ; 62(3)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38389246

RESUMO

Candida albicans is a dimorphic opportunistic pathogen in immunocompromised individuals. We have previously demonstrated that sodium houttuyfonate (SH), a derivative of medicinal herb Houttuynia cordata Thunb, was effective for antifungal purposes. However, the physical impediment of SH by C. albicans ß-glucan may weaken the antifungal activity of SH. In this study, the interactions of SH with cell wall (CW), extracellular matrix (EM), CW ß-glucan, and a commercial ß-glucan zymosan A (ZY) were inspected by XTT assay and total plate count in a standard reference C. albicans SC5314 as well as two clinical fluconazole-resistant strains Z4935 and Z5172. After treatment with SH, the content and exposure of CW ß-glucan, chitin, and mannan were detected, the fungal clearance by phagocytosis of RAW264.7 and THP-1 was examined, and the gene expressions and levels of cytokines TNF-ɑ and IL-10 were also monitored. The results showed that SH could be physically impeded by ß-glucan in CW, EM, and ZY. This impediment subsequently triggered the exposure of CW ß-glucan and chitin with mannan masked in a time-dependent manner. SH-induced ß-glucan exposure could significantly enhance the phagocytosis and inhibit the growth of C. albicans. Meanwhile, the SH-pretreated fungal cells could greatly stimulate the cytokine gene expressions and levels of TNF-ɑ and IL-10 in the macrophages. In sum, the strategy that the instant physical impediment of C. albicans CW to SH, which can induce the exposure of CW ß-glucan may be universal for C. albicans in response to physical deterrent by antifungal drugs.


Assuntos
Alcanos , Candida albicans , Sulfitos , beta-Glucanas , Humanos , Antifúngicos/uso terapêutico , beta-Glucanas/farmacologia , Interleucina-10/metabolismo , Interleucina-10/farmacologia , Fator de Necrose Tumoral alfa , Mananas , Fagocitose , Quitina/metabolismo , Parede Celular/metabolismo
15.
Microbiol Spectr ; 12(4): e0409523, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38376363

RESUMO

Candida albicans, one of the most prevalent human fungal pathogens, causes diverse diseases extending from superficial infections to deadly systemic mycoses. Currently, only three major classes of antifungal drugs are available to treat systemic infections: azoles, polyenes, and echinocandins. Alarmingly, the efficacy of these antifungals against C. albicans is hindered both by basal tolerance toward the drugs and the development of resistance mechanisms such as alterations of the drug's target, modulation of stress responses, and overexpression of efflux pumps. Thus, the need to identify novel antifungal strategies is dire. To address this challenge, we screened 3,049 structurally-diverse compounds from the Boston University Center for Molecular Discovery (BU-CMD) chemical library against a C. albicans clinical isolate and identified 17 molecules that inhibited C. albicans growth by >80% relative to controls. Among the most potent compounds were CMLD013360, CMLD012661, and CMLD012693, molecules representing two distinct chemical scaffolds, including 3-hydroxyquinolinones and a xanthone natural product. Based on structural insights, CMLD013360, CMLD012661, and CMLD012693 were hypothesized to exert antifungal activity through metal chelation. Follow-up investigations revealed all three compounds exerted antifungal activity against non-albicans Candida, including Candida auris and Candida glabrata, with the xanthone natural product CMLD013360 also displaying activity against the pathogenic mould Aspergillus fumigatus. Media supplementation with metallonutrients, namely ferric or ferrous iron, rescued C. albicans growth, confirming these compounds act as metal chelators. Thus, this work identifies and characterizes two chemical scaffolds that chelate iron to inhibit the growth of the clinically relevant fungal pathogen C. albicansIMPORTANCEThe worldwide incidence of invasive fungal infections is increasing at an alarming rate. Systemic candidiasis caused by the opportunistic pathogen Candida albicans is the most common cause of life-threatening fungal infection. However, due to the limited number of antifungal drug classes available and the rise of antifungal resistance, an urgent need exists for the identification of novel treatments. By screening a compound collection from the Boston University Center for Molecular Discovery (BU-CMD), we identified three compounds representing two distinct chemical scaffolds that displayed activity against C. albicans. Follow-up analyses confirmed these molecules were also active against other pathogenic fungal species including Candida auris and Aspergillus fumigatus. Finally, we determined that these compounds inhibit the growth of C. albicans in culture through iron chelation. Overall, this observation describes two novel chemical scaffolds with antifungal activity against diverse fungal pathogens.


Assuntos
Produtos Biológicos , Micoses , Xantonas , Humanos , Candida albicans , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Micoses/tratamento farmacológico , Farmacorresistência Fúngica , Quelantes/farmacologia , Quelantes/uso terapêutico , Aspergillus fumigatus , Ferro , Xantonas/uso terapêutico , Testes de Sensibilidade Microbiana
16.
Oral Dis ; 30(7): 4740-4750, 2024 10.
Artigo em Inglês | MEDLINE | ID: mdl-38287486

RESUMO

OBJECTIVE: This study proposed to assess the effect of Cryptocarya moschata extract on single and mixed biofilms formed on denture base and reline acrylic resin. MATERIALS AND METHODS: Single and mixed biofilms of Candida albicans and Streptococcus mutans were formed on the samples and treated with C. moschata extract; Nystatin solution at 100,000 IU/mL or Penicillin antibiotic solution at 100,000 IU/mL; or PBS solution. Antimicrobial activity was analyzed by counting colony-forming units, metabolism assay, assessment of protein components of the biofilm matrix, and of cell viability using confocal laser scanning microscopy (CLSM). Data were submitted to ANOVA and Tukey's post-test (α = 0.05). RESULTS: Cryptocarya moschata extract reduced cell viability of C. albicans and S. mutans single and mixed biofilms formed on samples. For all types of biofilms in the C. moschata group, there was a log reduction of the biofilm, proven by the Alamar Blue assay. Analyzing the extracellular matrix protein components, groups treated with the extract exhibited a lower level of fluorescence compared to the PBS groups. Reduction in thickness biofilm and viable cells was perceptible in the C. moschata group when assessing through CLSM. CONCLUSION: Cryptocarya moschata extract reduced the single and mixed biofilms of C. albicans and S. mutans on acrylic resins.


Assuntos
Resinas Acrílicas , Biofilmes , Candida albicans , Bases de Dentadura , Extratos Vegetais , Streptococcus mutans , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Resinas Acrílicas/farmacologia , Streptococcus mutans/efeitos dos fármacos , Extratos Vegetais/farmacologia , Bases de Dentadura/microbiologia , Microscopia Confocal , Nistatina/farmacologia
17.
J Dent ; 143: 104867, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38286192

RESUMO

OBJECTIVES: This study aimed to evaluate silver nanoparticles (AgNPs) obtained by a 'green' route associated or not to tyrosol (TYR) against Streptococcus mutans and Candida albicans in planktonic and biofilms states. METHODS: AgNPs were obtained by a 'green' route using pomegranate extract. The minimum inhibitory concentration (MIC) against S. mutans and C. albicans was determined for AgNPs and TYR combined and alone, and fractional inhibitory concentration index (FICI) was calculated. Single biofilms of C. albicans and S. mutans were cultivated for 24 h and then treated with drugs alone or in combination for 24 h. RESULTS: AgNPs and TYR were effective against C. albicans and S. mutans considering planktonic cells alone and combined. The MIC values obtained for C. albicans was 312.5 µg/mL (AgNPs) and 50 mM (TYR) and for S. mutans was 78.1 µg/mL (AgNPs) and 90 mM (TYR). The combination of these antimicrobial agents was also effective against both microorganisms: 2.44 µg/mL/0.08 mM (AgNPs/TYR) for C. albicans and 39.05 µg/mL /1.25 mM (AgNPs/TYR) for S. mutans. However, synergism was observed only for C. albicans (FICI 0.008). When biofilm was evaluated, a reduction of 4.62 log10 was observed for S. mutans biofilm cells treated with AgNPs (p < 0.05, Tukey test). However, the addition of TYR to AgNPs did not improve their action against biofilm cells (p > 0.05). AgNPs combined with TYR demonstrated a synergistic effect against C. albicans biofilms. CONCLUSIONS: These findings suggest the potential use of AgNPs with or without TYR against C. albicans and S. mutans, important oral pathogens. CLINICAL SIGNIFICANCE: AgNPs obtained by a 'green' route combined or not with TYR can be an alternative to develop several types of oral antimicrobial therapies and biomaterials.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Álcool Feniletílico , Álcool Feniletílico/análogos & derivados , Prata/farmacologia , Anti-Infecciosos/farmacologia , Álcool Feniletílico/farmacologia , Candida albicans , Biofilmes , Streptococcus mutans
18.
Phytomedicine ; 124: 155306, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38176270

RESUMO

BACKGROUND: Most bacteria and fungi form biofilms that attach to living or abiotic surfaces. These biofilms diminish the efficacy of antimicrobial agents and contribute to chronic infections. Furthermore, multispecies biofilms composed of bacteria and fungi are often found at chronic infection sites. PURPOSE: In this study, lawsone (2­hydroxy-1,4-naphthoquinone) and its parent 1,4-naphthoquinone were studied for antimicrobial and antibiofilm activities against single-species and multispecies biofilms of enterohemorrhagic Escherichia coli O157:H7 (EHEC) and Candida albicans. METHODS: Biofilm formation assays, biofilm eradication assays, antimicrobial assays, live cell imaging microscopy, confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), extracellular polymeric substances and indole production, cell surface hydrophilicity assay, cell motility, cell aggregation, hyphal growth, dual species biofilm formation, quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and toxicity assays on plant seed germination and nematode model were utilized to investigate how lawsone affect biofilm development. RESULTS: Sub-inhibitory concentrations of lawsone (35 µg/ml) significantly inhibited single-and multispecies biofilm development. Lawsone reduced the production of curli and indole, and the swarming motility of EHEC, efficiently inhibited C. albicans cell aggregation and hyphal formation, and increased the cell surface hydrophilicity of C. albicans. Transcriptomic analysis showed that lawsone suppressed the expression of the curli-related genes csgA and csgB in EHEC, and the expression of several hypha- and biofilm-related genes (ALS3, ECE1, HWP1, and UME6) in C. albicans. In addition, lawsone up to 100 µg/ml was nontoxic to the nematode Caenorhabditis elegans and to the seed growth of Brassica rapa and Triticum aestivum. CONCLUSION: These results show that lawsone inhibits dual biofilm development and suggest that it might be useful for controlling bacterial or fungal infections and multispecies biofilms.


Assuntos
Anti-Infecciosos , Escherichia coli O157 , Naftoquinonas , Candida albicans , Biofilmes , Indóis/farmacologia
19.
Int J Artif Organs ; 47(3): 223-226, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38281934

RESUMO

With rates of ECMO utilization on the rise, prevention of nosocomial infections is of paramount importance. Candida auris, an emerging highly pathogenic multidrug resistant fungus, is of particular concern as it is associated with persistent colonization of environmental surfaces, inability to be recognized by many diagnostic platforms, inconsistent laboratory susceptibility results, and high mortality rates. We describe a case of C. auris in a VV-ECMO patient successfully managed with a combination of anidulafungin, amphotericin B, and flucytosine.


Assuntos
Antifúngicos , Candida auris , Humanos , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Candida , Testes de Sensibilidade Microbiana
20.
Microb Cell Fact ; 23(1): 20, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218907

RESUMO

The increasing interest in environmental protection laws has compelled companies to regulate the disposal of waste organic materials. Despite efforts to explore alternative energy sources, the world remains heavily dependent on crude petroleum oil and its derivatives. The expansion of the petroleum industry has significant implications for human and environmental well-being. Bioremediation, employing living microorganisms, presents a promising approach to mitigate the harmful effects of organic hydrocarbons derived from petroleum. This study aimed to isolate and purify local yeast strains from oil-contaminated marine water samples capable of aerobically degrading crude petroleum oils and utilizing them as sole carbon and energy sources. One yeast strain (isolate B) identified as Candida tropicalis demonstrated high potential for biodegrading petroleum oil in seawater. Physiological characterization revealed the strain's ability to thrive across a wide pH range (4-11) with optimal growth at pH 4, as well as tolerate salt concentrations ranging from 1 to 12%. The presence of glucose and yeast extract in the growth medium significantly enhanced the strain's biomass formation and biodegradation capacity. Scanning electron microscopy indicated that the yeast cell diameter varied based on the medium composition, further emphasizing the importance of organic nitrogenous sources for initial growth. Furthermore, the yeast strain exhibited remarkable capabilities in degrading various aliphatic and aromatic hydrocarbons, with a notable preference for naphthalene and phenol at 500 and 1000 mg/l, naphthalene removal reached 97.4% and 98.6%, and phenol removal reached 79.48% and 52.79%, respectively. Optimization experiments using multi-factorial sequential designs highlighted the influential role of oil concentration on the bioremediation efficiency of Candida tropicalis strain B. Moreover, immobilized yeast cells on thin wood chips demonstrated enhanced crude oil degradation compared to thick wood chips, likely due to increased surface area for cell attachment. These findings contribute to our understanding of the potential of Candida tropicalis for petroleum oil bioremediation in marine environments, paving the way for sustainable approaches to address oil pollution.


Assuntos
Candida tropicalis , Petróleo , Humanos , Candida tropicalis/metabolismo , Biodegradação Ambiental , Leveduras/metabolismo , Petróleo/metabolismo , Hidrocarbonetos/metabolismo , Fenol/metabolismo , Naftalenos/metabolismo
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