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1.
Front Cell Infect Microbiol ; 14: 1397724, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966251

RESUMO

Cryptococcus neoformans is at the top of the list of "most wanted" human pathogens. Only three classes of antifungal drugs are available for the treatment of cryptococcosis. Studies on antifungal resistance mechanisms are limited to the investigation of how a particular antifungal drug induces resistance to a particular drug, and the impact of stresses other than antifungals on the development of antifungal resistance and even cross-resistance is largely unexplored. The endoplasmic reticulum (ER) is a ubiquitous subcellular organelle of eukaryotic cells. Brefeldin A (BFA) is a widely used chemical inducer of ER stress. Here, we found that both weak and strong selection by BFA caused aneuploidy formation in C. neoformans, mainly disomy of chromosome 1, chromosome 3, and chromosome 7. Disomy of chromosome 1 conferred cross-resistance to two classes of antifungal drugs: fluconazole and 5-flucytosine, as well as hypersensitivity to amphotericin B. However, drug resistance was unstable, due to the intrinsic instability of aneuploidy. We found overexpression of AFR1 on Chr1 and GEA2 on Chr3 phenocopied BFA resistance conferred by chromosome disomy. Overexpression of AFR1 also caused resistance to fluconazole and hypersensitivity to amphotericin B. Furthermore, a strain with a deletion of AFR1 failed to form chromosome 1 disomy upon BFA treatment. Transcriptome analysis indicated that chromosome 1 disomy simultaneously upregulated AFR1, ERG11, and other efflux and ERG genes. Thus, we posit that BFA has the potential to drive the rapid development of drug resistance and even cross-resistance in C. neoformans, with genome plasticity as the accomplice.


Assuntos
Aneuploidia , Antifúngicos , Brefeldina A , Cryptococcus neoformans , Farmacorresistência Fúngica , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/genética , Brefeldina A/farmacologia , Antifúngicos/farmacologia , Farmacorresistência Fúngica/genética , Fluconazol/farmacologia , Anfotericina B/farmacologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Testes de Sensibilidade Microbiana , Flucitosina/farmacologia , Humanos , Estresse do Retículo Endoplasmático/efeitos dos fármacos
2.
J Mass Spectrom Adv Clin Lab ; 33: 7-13, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38974659

RESUMO

Background: As an active metabolite of a commonly prescribed immunosuppressant, mycophenolic acid (MPA) levels are often monitored to prevent organ rejection following a transplant. Triazoles are often prescribed for treatment of invasive fungal infections in immunocompromised patients. Due to the variability in individual pharmacokinetics and drug-drug interactions, therapeutic drug monitoring is recommended for triazole antifungals. A multiplex LC-MS/MS assay has been developed that can quantify both MPA and triazole drugs in serum. Methods: A sample preparation procedure was established to spike in internal standard compounds and precipitate proteins. Reversed-phase chromatographic separation was performed on a C18 column with an analysis time of five minutes per sample. The mass spectrometer was operated in multiple reaction monitoring mode. The method was validated on two HPLC systems interfaced with either a Triple Quad 6500 or an API 4000 instrument. Results: The multiplex assay was linear over a wide dynamic range with analyte measurable ranges of 0.4-48 µg/mL for MPA, 0.1-12 µg/mL for posaconazole, and 0.2-24 µg/mL for voriconazole, itraconazole, hydroxyitraconazole, and isavuconazole. The between-day and intraday imprecisions were less than 10 %. Limits of detection were below 0.04 ug/mL with limits of quantitation below 0.2 µg/mL. Method comparison studies against the current in-house method met acceptance criteria. The instrument comparison study demonstrated a strong correlation between data collected from the two systems. Conclusion: A robust multiplex LC-MS/MS assay was developed and validated for monitoring MPA and triazoles drug levels in a clinical laboratory. The assay performance on two distinct instruments was acceptable and comparable.

3.
Curr Res Microb Sci ; 7: 100247, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974670

RESUMO

The incidence of invasive fungal infections caused by Candida species is increasing, particularly in immunocompromised individuals. This increasing incidence poses a dual challenge, comprising escalating antifungal resistance and the necessity for accurate fungal identification. The Candida haemulonii complex further complicates these challenges due to limited identification tools. Like some other Candida species, infections involving this complex show resistance to multiple antifungals, requiring innovative therapeutic approaches. Rapamycin, known for its antifungal properties and immunosuppressive characteristics, was investigated against the C. haemulonii complex species. Results revealed a rapamycin minimal inhibitory concentration (MIC) range of 0.07 to >20 µM, with fungicidal effects in most strains. In vitro analyses using the rapamycin maximum plasma concentration (0.016 µM) showed reduced surface properties and decreased production of extracellular enzymes. Rapamycin also hindered biofilm formation by some strains. Even when treated at the human therapeutic dose, which is lower than the MIC, phenotypic variations in C. haemulonii were detected, hinting at the possible attenuation of some virulence factors when exposed to rapamycin.

4.
Respir Med Case Rep ; 51: 102071, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974754

RESUMO

An elderly woman with a history of myelodysplastic syndrome complicated by cavitary pneumonia treated with antibiotics and antifungal therapy was admitted with severe sepsis and pulmonary opacities on imaging. Pulmonary infection with Scedosporium prolificans, was diagnosed on bronchopulmonary lavage (BAL). This common environmental fungus is known to cause rare but severe infection in immunocompromised hosts. The patient was diagnosed with progression to acute myeloid leukemia during the hospitalization for which chemotherapy was initiated. Despite broadening antifungal therapy, the patient developed multi-organ system failure and died.

5.
Future Microbiol ; : 1-11, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979570

RESUMO

Aim: To develop a ß-AgVO3 gel and evaluate its physicochemical stability and antifungal activity against Candida albicans. Materials & methods: The gel was prepared from the minimum inhibitory concentration (MIC) of ß-AgVO3. The physicochemical stability was evaluated by centrifugation, accelerated stability (AS), storage (St), pH, syringability, viscosity and spreadability tests and antifungal activity by the agar diffusion. Results: The MIC was 62.5 µg/ml. After centrifugation, AS and St gels showed physicochemical stability. Lower viscosity and higher spreadability were observed for the higher ß-AgVO3 concentration and the minimum force for extrusion was similar for all groups. Antifungal effect was observed only for the ß-AgVO3 gel with 20xMIC. Conclusion: The ß-AgVO3 gel showed physicochemical stability and antifungal activity.


We used silver and vanadium to make a gel that can kill fungi in the mouth. We looked at the color of the gel, it's smell and also checked how well it lasted. The gel turned yellow and had no smell and did not spoil for at least 2 months. When we tested the gel against a type of fungus, it worked as well as another medicine called chlorhexidine, which is sold in pharmacies. But when we compared it with another medicine called nystatin, our gel was not as effective in killing the fungus.

6.
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
7.
Structure ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38964337

RESUMO

Ceramide synthases (CerSs) play crucial roles in sphingolipid metabolism and have emerged as promising drug targets for metabolic diseases, cancers, and antifungal therapy. However, the therapeutic targeting of CerSs has been hindered by a limited understanding of their inhibition mechanisms by small molecules. Fumonisin B1 (FB1) has been extensively studied as a potent inhibitor of eukaryotic CerSs. In this study, we characterize the inhibition mechanism of FB1 on yeast CerS (yCerS) and determine the structures of both FB1-bound and N-acyl-FB1-bound yCerS. Through our structural analysis and the observation of N-acylation of FB1 by yCerS, we propose a potential ping-pong catalytic mechanism for FB1 N-acylation by yCerS. Lastly, we demonstrate that FB1 exhibits lower binding affinity for yCerS compared to the C26- coenzyme A (CoA) substrate, suggesting that the potent inhibitory effect of FB1 on yCerS may primarily result from the N-acyl-FB1 catalyzed by yCerS, rather than through direct binding of FB1.

8.
Int J Environ Health Res ; : 1-22, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38965904

RESUMO

The present investigation examines the antimicrobial and antifungal characteristics of natural deep eutectic solvents (NADES) and apple vinegar in relation to a diverse array of bacterial and fungal strains. The clinical bacterial strains, including gram-negative and gram-positive, and the fungal pathogen Candida albicans, were subjected to solid medium diffusion to determine the inhibitory effects of these compounds. The results show that NADES has superior antimicrobial and antifungal action compared to apple vinegar. The observed inhibitory zones for apple vinegar and NADES varied in length from 16.5 to 24.2 and 16 to 52.5 mm, respectively. The results obtained indicate that no synergy is observed for this mixture (50% AV + 50% NADES). The range of values for bactericidal concentrations (MBC) and minimal inhibitory concentrations (MIC) was 0.0125 to 0.2 and 0.0125 to 0.4 µl/ml, respectively. Antibacterial and antifungal chemicals may be found in apple vinegar and NADES, with NADES offering environmentally safe substitutes for traditional antibiotics. Additional investigation is suggested to refine these compounds for a wide range of bacteria, which could create antimicrobial solutions that are both highly effective and specifically targeted, thereby offering extensive potential in medicine and the environment.

9.
J Med Microbiol ; 73(7)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38967406

RESUMO

Introduction. Cold plasma is frequently utilized for the purpose of eliminating microbial contaminants. Under optimal conditions, it can function as plasma medicine for treating various diseases, including infections caused by Candida albicans, an opportunistic pathogen that can overgrow in individuals with weakened immune system.Gap Statement. To date, there has been less molecular study on cold plasma-treated C. albicans.Research Aim. The study aims to fill the gap in understanding the molecular response of C. albicans to cold plasma treatment.Methodology. This project involved testing a cold plasma generator to determine its antimicrobial effectiveness on C. albicans' planktonic cells. Additionally, the cells' transcriptomics responses were investigated using RNA sequencing at various treatment durations (1, 3 and 5 min).Results. The results show that our cold plasma effectively eliminates C. albicans. Cold plasma treatment resulted in substantial downregulation of important pathways, such as 'nucleotide metabolism', 'DNA replication and repair', 'cell growth', 'carbohydrate metabolism' and 'amino acid metabolism'. This was an indication of cell cycle arrest of C. albicans to preserve energy consumption under unfavourable conditions. Nevertheless, C. albicans adapted its GSH antioxidant system to cope with the oxidative stress induced by reactive oxygen species, reactive nitrogen species and other free radicals. The treatment likely led to a decrease in cell pathogenicity as many virulence factors were downregulated.Conclusion. The study demonstrated the major affected pathways in cold plasma-treated C. albicans, providing valuable insights into the molecular response of C. albicans to cold plasma treatment. The findings contribute to the understanding of the antimicrobial efficiency of cold plasma and its potential applications in the field of microbiology.


Assuntos
Candida albicans , Perfilação da Expressão Gênica , Gases em Plasma , Candida albicans/genética , Candida albicans/efeitos dos fármacos , Gases em Plasma/farmacologia , Plâncton/genética , Transcriptoma , Estresse Oxidativo , Regulação Fúngica da Expressão Gênica , Espécies Reativas de Oxigênio/metabolismo , Humanos
10.
Med Chem ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38982919

RESUMO

BACKGROUND: Among various carboxylic acid derivatives, valeric acid or pentanoic acid is found to be widely distributed in nature. It is a straight-chain alkyl carboxylic acid containing five carbon atoms. Due to the therapeutic value of valeric acid, it is used as a versatile nucleus in the pharmaceutical field. Valeric acid derivatives are associated with a broad spectrum of biological activities, like anticonvulsant, antiplatelet, antidiabetic, and plant growth activities. AIM: It has previously been revealed that peptide derivatives of carboxylic acids are accountable for enhanced antimicrobial activity. Therefore, it was hypothesized that coupling peptides with valeric acid would increase the antimicrobial properties of the target compounds. So, the objective of the present study was to synthesize peptide derivatives of 5-bromovaleric acid and evaluate their antibacterial and antifungal activities. METHODS: 5-bromovaleric acid was synthesized by the reaction of cyclopentanone and hydrogen peroxide in the presence of copper bromide and sodium bromide. Additionally, 5-bromovaleric acid was coupled with amino acid methyl esters, dipeptides, tripeptides, and tetrapeptides in the presence of dicyclohexylcarbodimide (DCC) and N-methylmorpholine (NMM) as a base under continuous stirring for 36 hours to produce its peptide derivatives. RESULTS: The results obtained showed that 5-bromovaleric acid possesses more potent antibacterial activity than N-terminal 5-bromovaleric acid conjugates of selected di-, tri, and tetra peptide Cterminal methyl esters against ciprofloxacin as a standard. The selected dipeptide and tripeptide Nterminal 5-bromovaleric acid-conjugated C-terminal methyl ester derivatives were more active than the selected tetrapeptide methyl ester analogue. Using fluconazole as a reference, the antifungal efficacy of 5-bromovaleric acid against C. albicans and A. niger declined as it was combined with C-terminal methyl esters of selected dipeptides, tripeptides, and tetrapeptides. CONCLUSION: The novel selected peptide derivatives had less antibacterial and antifungal action than the parent 5-bromovaleric acid. Antibacterial and antifungal investigations showed that 5- bromopentanoic acid peptide derivatives might impair antimicrobial efficacy. Further, attaching 5- bromopentanoic acid to di, tri, and tetra peptides did not boost their antibacterial potential.

11.
Int J Biol Macromol ; 275(Pt 2): 133627, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964684

RESUMO

Nanoemulsions are a promising alternative for essential oil incorporation into active coatings. The influence of the preparation steps order on nanoemulsions' physical properties is still little explored. This study aimed to analyze the effect of the sequence of preparation steps and of the oil and polymer concentration on the stability, physical properties, and antifungal activity of alginate-based cinnamon essential oil nanoemulsions. The nanoemulsions were produced by two strategies: (I) preparation directly into an alginate solution (Ultra-Turrax at 10,000 rpm for 5 min + Ultrasound 150 W for 3 min); and (II) preparation in water (Ultra-Turrax at 10,000 rpm for 5 min + Ultrasound 150 W for 3 min) followed by homogenization with a sodium alginate solution (Ultra-Turrax at 10,000 rpm for 1, 3 or 5 min). The nanoemulsion prepared by the second strategy showed better stability, physical properties, and antifungal activity. In general, the presence of alginate hindered the cavitation effects of ultrasound, leading to the increase of droplets size and consequently affecting emulsions stability, turbidity, and antifungal properties.

12.
Front Med (Lausanne) ; 11: 1397539, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978781

RESUMO

Disseminated candidiasis is a severe complication in patients with hematological malignancies who have undergone chemotherapy or hematopoietic stem cell transplantation. It has a high mortality rate. When disseminated candidiasis caused by Candida tropicalis involves either the brain or heart, the prognosis is extremely poor. Traditional methods such as cultures are limited in diagnosing disseminated candidiasis. We describe a case report of a 55-year-old man with acute myeloid leukemia who developed candidemia caused by Candida tropicalis after chemotherapy, which disseminated extensively to the heart, brain, skin, liver, spleen and kidneys. In this instance, the patient was rapidly diagnosed with candida infection by metagenomic next generation sequencing, and successfully treated with combination therapy of isavuconazole and amphotericin B. The patient continued with treatment of leukemia while simultaneously receiving antifungal therapy, and both leukemia and disseminated candidiasis were effectively controlled. This case report provides real-world experience for treatment of patients with leukemia complicated by disseminated candidiasis.

13.
J Med Case Rep ; 18(1): 301, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38951939

RESUMO

BACKGROUND: Pulmonary aspergillosis is a prevalent opportunistic fungal infection that can lead to mortality in pediatric patients with underlying immunosuppression. Appropriate and timely treatment of pulmonary aspergillosis can play a crucial role in reducing mortality among children admitted with suspected infections. CASE PRESENTATION: The present study reports three cases of inappropriate treatment of pulmonary aspergillosis caused by Aspergillus flavus in two Iranian pediatric patients under investigation and one Afghan patient. Unfortunately, two of them died. The cases involved patients aged 9, 1.5, and 3 years. They had been diagnosed with pulmonary disorders, presenting nonspecific clinical signs and radiographic images suggestive of pneumonia. The identification of A. flavus was confirmed through DNA sequencing of the calmodulin (CaM) region. CONCLUSION: A. flavus was the most prevalent cause of pulmonary aspergillosis in pediatric patients. Early diagnosis and accurate antifungal treatment of pulmonary aspergillosis could be crucial in reducing the mortality rate and also have significant potential for preventing other complications among children. Moreover, antifungal prophylaxis seems to be essential for enhancing survival in these patients.


Assuntos
Antifúngicos , Aspergillus flavus , Aspergilose Pulmonar , Humanos , Aspergillus flavus/isolamento & purificação , Antifúngicos/uso terapêutico , Criança , Masculino , Pré-Escolar , Aspergilose Pulmonar/tratamento farmacológico , Aspergilose Pulmonar/diagnóstico , Lactente , Feminino , Evolução Fatal , Irã (Geográfico)
14.
Drug Des Devel Ther ; 18: 2531-2553, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952486

RESUMO

The WHO Global Status Report on Oral Health 2022 reveals that oral diseases caused by infection with oral pathogenic microorganisms affect nearly 3.5 billion people worldwide. Oral health problems are caused by the presence of S. mutans, S. sanguinis, E. faecalis and C. albicans in the oral cavity. Synthetic anti-infective drugs have been widely used to treat oral infections, but have been reported to cause side effects and resistance. Various strategies have been implemented to overcome this problem. Synthetic anti-infective drugs have been widely used to treat oral infections, but they have been reported to cause side effects and resistance. Therefore, it is important to look for safe anti-infective alternatives. Ethnobotanical and ethnopharmacological studies suggest that Red Betel leaf (Piper crocatum Ruiz & Pav) could be a potential source of oral anti-infectives. This review aims to discuss the pathogenesis mechanism of several microorganisms that play an important role in causing health problems, the mechanism of action of synthetic oral anti-infective drugs in inhibiting microbial growth in the oral cavity, and the potential of red betel leaf (Piper crocatum Ruiz & Pav) as an herbal oral anti-infective drug. This study emphasises the importance of researching natural components as an alternative treatment for oral infections that is more effective and can meet global needs.


Assuntos
Piper , Humanos , Piper/química , Doenças da Boca/tratamento farmacológico , Doenças da Boca/microbiologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Boca/microbiologia
15.
Braz J Microbiol ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954219

RESUMO

Fusarium oxysporum is a cross-kingdom pathogen that infects humans, animals, and plants. The primary concern regarding this genus revolves around its resistance profile to multiple classes of antifungals, particularly azoles. However, the resistance mechanism employed by Fusarium spp. is not fully understood, thus necessitating further studies to enhance our understanding and to guide future research towards identifying new drug targets. Here, we employed an untargeted proteomic approach to assess the differentially expressed proteins in a soil isolate of Fusarium oxysporum URM7401 cultivated in the presence of amphotericin B and fluconazole. In response to antifungals, URM7401 activated diverse interconnected pathways, such as proteins involved in oxidative stress response, proteolysis, and lipid metabolism. Efflux proteins, antioxidative enzymes and M35 metallopeptidase were highly expressed under amphotericin B exposure. Antioxidant proteins acting on toxic lipids, along with proteins involved in lipid metabolism, were expressed during fluconazole exposure. In summary, this work describes the protein profile of a resistant Fusarium oxysporum soil isolate exposed to medical antifungals, paving the way for further targeted research and discovering new drug targets.

16.
Int Microbiol ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38955904

RESUMO

The study aimed to investigate Candida albicans presence, antifungal resistance, biofilm formation, putative virulence genes, and molecular characterization in oral samples of dogs and cats. A total of 239 oral samples were collected from cats and dogs of various breeds and ages at Erciyes University, Faculty of Veterinary Medicine Clinics, between May 2017 and April 2018. Among 216 isolates obtained, 15 (6.95%) were identified as C. albicans, while 8 (3.7%) were non-albicans Candida species. Antifungal susceptibility testing revealed sensitivities to caspofungin, fluconazole, and flucytosine in varying proportions. Molecular analysis indicated the presence of fluconazole and caspofungin resistance genes in all C. albicans isolates. Additionally, virulence genes ALS1, HWP1, and HSP90 showed variable presence. Biofilm formation varied among isolates, with 46.7% strong, 33.3% moderate, and 20% weak producers. PCA analysis categorized isolates into two main clusters, with some dog isolates grouped separately. The findings underscore the significance of oral care and protective measures in pets due to C. albicans prevalence, biofilm formation, virulence factors, and antifungal resistance in their oral cavity, thereby aiding clinical diagnosis and treatment in veterinary medicine.

17.
Antimicrob Agents Chemother ; : e0022524, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958455

RESUMO

As comparative pharmacokinetic/pharmacodynamic (PK/PD) studies of liposomal amphotericin B (L-AMB) against Candida spp. are lacking, we explored L-AMB pharmacodynamics against different Candida species in an in vitro PK/PD dilution model. Eight Candida glabrata, Candida parapsilosis, and Candida krusei isolates (EUCAST/CLSI AMB MIC 0.125-1 mg/L) were studied in the in vitro PK/PD model simulating L-AMB Cmax = 0.25-64 mg/L and t1/2 = 9 h. The model was validated with one susceptible and one resistant Candida albicans isolate. The Cmax/MIC-log10CFU/mL reduction from the initial inoculum was analyzed with the Emax model, and Monte Carlo analysis was performed for the standard (3 mg/kg with Cmax = 21.87 ± 12.47 mg/L) and higher (5 mg/kg with Cmax = 83 ± 35.2 mg/L) L-AMB dose. A ≥1.5 log10CFU/mL reduction was found at L-AMB Cmax = 8 mg/L against C. albicans, C. parapsilosis, and C. krusei isolates (MIC 0.25-0.5 mg/L) whereas L-AMB Cmax ≥ 32 mg/L was required for C. glabrata isolates. The in vitro PK/PD relationship followed a sigmoidal pattern (R2 ≥ 0.85) with a mean Cmax/MIC required for stasis of 2.1 for C. albicans (close to the in vivo stasis), 24/17 (EUCAST/CLSI) for C. glabrata, 8 for C. parapsilosis, and 10 for C. krusei. The probability of target attainment was ≥99% for C. albicans wild-type (WT) isolates with 3 mg/kg and for wild-type isolates of the other species with 5 mg/kg. L-AMB was four- to eightfold less active against the included non-C. albicans species than C. albicans. A standard 3-mg/kg dose is pharmacodynamically sufficient for C. albicans whereas our data suggest that 5 mg/kg may be recommendable for the included non-C. albicans species.

18.
Nat Prod Res ; : 1-8, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958658

RESUMO

Hinokitiol is a natural broad-spectrum antimicrobial monoterpenoid, which is widely used as an antiseptic in food, cosmetics and other products. In the present study, the toxic actions of hinokitiol to the plant pathogen Sclerotinia sclerotiorum were investigated. The EC50 value for mycelial growth inhibition was 2.63 µg/mL, and there was no positive or negative cross-resistance between hinokitiol and carbendazim. The emulsifiable concentrate of 30% hinokitiol was prepared, which has excellent application prospect in the prevention of sclerotinia and gray mould. Hinokitiol is a promising spray fungicide for stems and leaves rather than seeds and roots.

19.
J Microbiol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958871

RESUMO

Fleagrass, a herb known for its pleasant aroma, is widely used as a mosquito repellent, antibacterial agent, and for treating colds, reducing swelling, and alleviating pain. The antifungal effects of the essential oils of fleagrass and carvacrol against Candida albicans were investigated by evaluating the growth and the mycelial and biofilm development of C. albicans. Transmission electron microscopy was used to evaluate the integrity of the cell membrane and cell wall of C. albicans. Fleagrass exhibited high fungicidal activity against C. albicans at concentrations of 0.5% v/v (via the Ras1/cAMP/PKA pathway). Furthermore, transmission electron microscopy revealed damage to the cell wall and membrane after treatment with the essential oil, which was further confirmed by the increased levels of ß-1,3-glucan and chitin in the cell wall. This study showed that fleagrass exerts good fungicidal and hyphal growth inhibition activity against C. albicans by disrupting its cell wall, and thus, fleagrass may be a potential antifungal drug.

20.
J Fluoresc ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958905

RESUMO

Pedalium Murex leaf extract was used in this study to create Nickel-doped Cerium oxide (Ni-CeO2) nanoparticles at 3 mol% and 5 mol% molar concentrations. The biosynthesized process was applied for the fabrication of Ni-CeO2 NPs. The X-ray diffraction method was used to identify their crystal structure. The XRD measurements showed that the Ni-CeO2 NPs crystallized into the face-centred cubic system. Fourier transform infrared spectral study was applied to explore the molecular vibrations and chemical bonding. The surface texture and chemical ingredients of Ni-CeO2 NPs were studied using field-emission scanning electron microscopy and energy-dispersive X-ray analysis. The EDX mapping spectra illustrate the uniform dispersal of Ce, Ni, and O atoms over the sample's surface. X-ray photoelectron spectroscopy (XPS) was conducted to confirm the chemical state of the Ni-CeO2 NPs. UV-Vis spectrum study was performed to ascertain the photon absorption, bandgap, and Urbach edge of Ni-CeO2 NPs. Photoluminescence (PL) research has been used to study the light-emitting characteristic of Ni-CeO2 NPs. The emissive intensity transition corresponding to Ni-CeO2 NPs was found to increase with the dopant level. The CIE 1931 chromaticity map was plotted to find the aptness of the samples for optical uses. The antifungal ability of Ni-CeO2 NPs was evaluated against the fungi candida albicans and candida krusein with the agar well-diffusion process. The fungicidal activity of the 3 mol% Ni doped CeO2 nanoparticles has shown a maximum zone of inhibition. The experimental findings illustrate the utility of Ni-CeO2 NPs for optical and antifungal applications.

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