RESUMEN
Anthracnose caused by Colletotrichum scovillei is a significant disease of pepper, including in postharvest stage. Bacillus species represent a potential microbial resource for controlling postharvest plant diseases. Here, a strain HG-8-2 was obtained and identified as Bacillus velezensis through morphological, biochemical, physiological, and molecular analyses. The culture filtrate showed highly antifungal activity against C. scovillei both in vitro and on pepper fruit. Crude lipopeptide extracts, which had excellent stability, could effectively inhibit mycelial growth of C. scovillei with an EC50 value of 28.48 ± 1.45 µg mL-1 and inhibited conidial germination. Pretreatment with the extracts reduced the incidence and lesion size of postharvest anthracnose on pepper fruit. Analysis using propidium iodide staining, malondialdehyde content detection and scanning electron microscope observation suggested that the crude lipopeptide extracts harbored antifungal activity by damaging cell membranes and mycelial structures. The RNA-seq analysis conducted on C. scovillei samples treated with the extracts, as compared to untreated samples, revealed significant alterations in the expression of multiple genes involved in protein biosynthesis. Overall, these results demonstrated that B. velezensis HG-8-2 and its crude lipopeptide extracts exhibit highly antagonistic ability against C. scovillei, thereby offering an effective biological agent for the control of anthracnose in pepper fruit.
Asunto(s)
Bacillus , Capsicum , Colletotrichum , Frutas , Enfermedades de las Plantas , Colletotrichum/efectos de los fármacos , Colletotrichum/crecimiento & desarrollo , Capsicum/microbiología , Bacillus/genética , Bacillus/metabolismo , Bacillus/fisiología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Frutas/microbiología , Antifúngicos/farmacología , Antifúngicos/metabolismo , Esporas Fúngicas/efectos de los fármacos , Esporas Fúngicas/crecimiento & desarrollo , Lipopéptidos/farmacología , Lipopéptidos/metabolismo , Micelio/crecimiento & desarrollo , Micelio/efectos de los fármacos , Agentes de Control Biológico/farmacologíaRESUMEN
Antifungal-resistant dermatophytes (ARD) infection is a hotspot issue in clinical microbiology and the dermatology field. Trichophyton indotineae as the dominant species of dermatophyte with terbinafine-resistance or multidrug resistance, is easy to be missed detection clinically, which brings severe challenges to diagnosis and treatment. ARD infection cases have emerged in China, and it predicts a risk of transmission among human. Based on the existing medical evidence and research data, the Mycology Group of Combination of Traditional and Western Medicine Dermatology and Chinese AntifungalâResistant Dermatophytoses Expert Consensus Group organized experts to make consensus on the management of the infection. Here, the consensus formulated diagnosis and treatment recommendations, to raise attention to dermatophytes drug resistance problem, and expect to provide reference information for the clinical diagnosis, treatment, prevention and control.
Asunto(s)
Antifúngicos , Consenso , Farmacorresistencia Fúngica , Tiña , Humanos , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Arthrodermataceae/efectos de los fármacos , China , Tiña/tratamiento farmacológico , Tiña/microbiología , Tiña/diagnóstico , Trichophyton/efectos de los fármacos , Trichophyton/aislamiento & purificaciónRESUMEN
BACKGROUND: Cystic fibrosis (CF), an inherited autosomal recessive disorder, is linked with high morbidity and mortality rates due to bacteria, filamentous, yeast and black yeast-like fungi colonisation in the upper respiratory tract. Although Candida species are the most common fungi isolated from CF patients, azole-resistant Aspergillus fumigatus (ARAf) is a big concern for invasive aspergillosis. Notably, the exact prevalences of Aspergillus species and the prevalence of ARAf isolates among Iranian CF patients have yet to be previously reported and are unknown. We aimed to investigate the prevalence of ARAf isolates in CF patients among Iranian populations by focusing on molecular mechanisms of the mutations in the target gene. METHODS: The 1 year prospective study recovered 120 sputum samples from 103 CF patients. Of these, 55.1% (86/156) yielded Aspergillus species, screened for ARAf using plates containing itraconazole (4 mg/L) and voriconazole (1 mg/L). According to the CLSI-M38 guidelines, antifungal susceptibility testing was performed using the broth microdilution method. In all phenotypically resistant isolates, the target of azole agents, the cyp51A gene, was sequenced to detect any possible single nucleotide polymorphisms (SNP) mediating resistance. RESULTS: Of 120 samples, 101 (84.2%) were positive for filamentous fungi and yeast-like relatives, with 156 fungal isolates. The most common colonising fungi were Aspergillus species (55.1%, 86/156), followed by Candida species (39.8%, 62/156), Exophiala species (3.8%, 6/156) and Scedosporium species (1.3%, 2/156). Forty out of 86 (46.5%) were identified for section Fumigati, 36 (41.9%) for section Flavi, 6 (7%) for section Nigri and 4 (4.6%) for section Terrei. Fourteen out of 40 A. fumigatus isolates were phenotypically resistant. The overall proportion of ARAf in total fungal isolates was 9% (14/156). cyp51A gene analysis in resistant isolates revealed that 13 isolates harboured G448S, G432C, T289F, D255E, M220I, M172V, G138C, G54E and F46Y mutations and one isolate carried G448S, G432C, T289F, D255E, M220I, G138C, G54E and F46Y mutations. Additionally, this study detects two novel cyp51A single-nucleotide polymorphisms (I242V and D490E). CONCLUSIONS: This study first investigated ARAf isolates in Iranian CF patients. Due to a resistance rate of up to 9%, it is recommended that susceptibility testing of Aspergillus isolates from CF patients receiving antifungal treatment be a part of the routine diagnostic workup. However, extensive multicentre studies with a high volume of CF patients are highly warranted to determine the impact of ARAf on CF patients.
Asunto(s)
Antifúngicos , Aspergillus fumigatus , Azoles , Fibrosis Quística , Sistema Enzimático del Citocromo P-450 , Farmacorresistencia Fúngica , Proteínas Fúngicas , Pruebas de Sensibilidad Microbiana , Humanos , Fibrosis Quística/microbiología , Fibrosis Quística/complicaciones , Irán/epidemiología , Aspergillus fumigatus/efectos de los fármacos , Aspergillus fumigatus/genética , Aspergillus fumigatus/aislamiento & purificación , Farmacorresistencia Fúngica/genética , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Estudios Prospectivos , Prevalencia , Sistema Enzimático del Citocromo P-450/genética , Azoles/farmacología , Azoles/uso terapéutico , Proteínas Fúngicas/genética , Masculino , Femenino , Aspergilosis/microbiología , Aspergilosis/epidemiología , Aspergilosis/tratamiento farmacológico , Adulto , Niño , Adolescente , Polimorfismo de Nucleótido Simple , Adulto Joven , Esputo/microbiología , Itraconazol/farmacología , Voriconazol/farmacología , Voriconazol/uso terapéutico , Preescolar , MutaciónRESUMEN
Aspergillus carbonarius, a common food-contaminating fungus, produces ochratoxin A (OTA) and poses a risk to human health. This study aimed to assess the inhibitory activity of tea tree essential oil and its main components, Terpene-4-ol (T4), α-terpineol (αS), and 3-carene (3C) against A. carbonarius. The study showed αS and T4 were the main antifungal components of tea tree essential oil, which primarily inhibit A. carbonarius growth through cell membrane disruption, reducing antioxidant enzyme activities (catalase, peroxidase, superoxide dismutase) and interrupting the tricarboxylic acid cycle. Furthermore, αS and T4 interacted with enzymes related to OTA biosynthesis. Molecular docking and molecular dynamics show that they bound mainly to P450 with a minimum binding energy of -7.232 kcal/mol, we infered that blocking the synthesis of OTA precursor OTß. Our hypothesis was preliminarily verified by the detection of key substances in the OTA synthesis pathway. The results of UHPLC-QTOF-MS2 analysis demonstrated that T4 achieved a degradation rate of 43 % for OTA, while αS reached 29.6 %, resulting in final breakdown products such as OTα and phenylalanine. These results indicated that α-terpinol and Terpene-4-ol have the potential to be used as naturally safe and efficient preservatives or active packaging to prevent OTA contamination.
Asunto(s)
Aspergillus , Monoterpenos Ciclohexánicos , Simulación del Acoplamiento Molecular , Ocratoxinas , Terpenos , Ocratoxinas/metabolismo , Ocratoxinas/biosíntesis , Aspergillus/metabolismo , Aspergillus/efectos de los fármacos , Terpenos/metabolismo , Aceite de Árbol de Té/farmacología , Aceite de Árbol de Té/química , Monoterpenos/farmacología , Monoterpenos/metabolismo , Antifúngicos/farmacología , Antifúngicos/química , Monoterpenos BicíclicosRESUMEN
We describe for the first time, a high-quality genome for a rare human yeast pathogen Candida mucifera, from a patient with chronic suppurative otitis media. This pathogen exhibited reduced azole susceptibility, similar to its close relatives within the Trichomonascus ciferrii species complex.
Asunto(s)
Candida , Genoma Fúngico , Otitis Media , Secuenciación Completa del Genoma , Humanos , Candida/genética , Candida/aislamiento & purificación , Candida/clasificación , Otitis Media/microbiología , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Azoles/farmacología , Pruebas de Sensibilidad Microbiana , Análisis de Secuencia de ADNRESUMEN
During the COVID-19 pandemic, fungal infections, especially pulmonary aspergillosis, mucormycosis, and invasive candidiasis, have emerged as a significant health concern. Beyond Candida albicans, the most common cause of invasive candidiasis, other rare ascomycetous yeast species have been described in tertiary care units, potentially posing a broader health threat. We have isolated, from September 2020 to June 2021, nine Diutina catenulata strains from urine samples of six patients. This was intriguing as this fungus had not been previously identified in our institution, nor after June 2021. Therefore, we decided to outline the clinical features of the patients with this rare pathogen, to describe phenotypic characteristics, including antifungal susceptibility profiles, of this yeast species and to identify the genetic makeup through whole-genome sequencing analysis to evaluate if this was a cluster of genetically similar D. catenulata isolates in our institution. The strains were identified through MALDI-TOF MS analyses and Sanger sequencing of two rDNA regions. All patients yielding D. catenulata from urine samples needed ventilator support and used urinary catheters during hospitalization for treatment of COVID-19. None of them had received COVID-19 vaccines. Morphological and biochemical profiles of the nine strains were largely consistent, although fluconazole susceptibility varied, ranging from 4 to 32 µg/mL. Phylogenomic analysis revealed minimal genetic variation among the isolates, with low intrapopulation variation, supported by the identification of only 84 SNPs across all strains. Therefore, we propose that the yeast strains isolated were part of a cluster of D. catenulata funguria in the context of COVID-19.
Asunto(s)
Antifúngicos , COVID-19 , SARS-CoV-2 , Centros de Atención Terciaria , Humanos , COVID-19/microbiología , COVID-19/epidemiología , Centros de Atención Terciaria/estadística & datos numéricos , Brasil/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , SARS-CoV-2/genética , SARS-CoV-2/efectos de los fármacos , Anciano , Adulto , Filogenia , Pruebas de Sensibilidad Microbiana , Saccharomycetales/genética , Saccharomycetales/aislamiento & purificación , Saccharomycetales/clasificación , Secuenciación Completa del GenomaRESUMEN
Wheat leaf blight caused by Bipolaris sorokiniana is a widespread fungal disease that poses a serious risk to wheat. Biological control without causing environmental pollution is one of the safest and most effective method to control plant diseases. The antagonistic bacterial strain HeN-7 (identified as Bacillus velezensis) was isolated from tobacco leaves cultivated in Henan province, China. The results of different concentrations of cell-free supernatant (CFS) from HeN-7 culture against B. sorokiniana mycelia showed that 20% HeN-7 CFS (v/v) reached the maximum inhibition rate of 96%. In the potted plants control assay, B. velezensis HeN-7 CFS exhibited remarkable biocontrol activity on the wheat infected with B. sorokiniana, the best pot control efficacy was 65% at 20% CFS. The research on the mechanism of action demonstrated that HeN-7 CFS induced the membrane lipid peroxidation in B. sorokiniana, leading to the disruption of cell membrane integrity and resulting in the leakage of cell contents; in addition, the intracellular mitochondrial membrane potential in mycelium dissipated and reactive oxygen species accumulated, thereby inhibiting the growth of B. sorokiniana. These results indicate that B. velezensis HeN-7 is a promising candidate as a biological control agent against Bipolaris sorokiniana infection.
Asunto(s)
Bacillus , Bipolaris , Nicotiana , Enfermedades de las Plantas , Hojas de la Planta , Bacillus/aislamiento & purificación , Bacillus/metabolismo , Bacillus/fisiología , Hojas de la Planta/microbiología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Nicotiana/microbiología , Triticum/microbiología , Antifúngicos/farmacología , Antifúngicos/metabolismo , China , Especies Reactivas de Oxígeno/metabolismo , Micelio/crecimiento & desarrollo , AntibiosisRESUMEN
Candida auris has emerged as a significant healthcare-associated pathogen due to its multidrug-resistant nature. Ongoing constraints in the discovery and provision of new antifungals create an urgent imperative to design effective remedies to this pressing global blight. Herein, we screened a chemical library and identified aryl-carbohydrazide analogs with potent activity against both C. auris and the most prevalent human fungal pathogen, C. albicans. SPB00525 [N'-(2,6-dichlorophenyl)-5-nitro-furan-2-carbohydrazide] exhibited potent activity against different strains that were resistant to standard antifungals. Using drug-induced haploinsufficient profiling, transcriptomics and metabolomic analysis, we uncovered that Ole1, a Δ(9) fatty acid desaturase, is the likely target of SPB00525. An analog of the latter, HTS06170 [N'-(2,6-dichlorophenyl)-4-methyl-1,2,3-thiadiazole-5-carbohydrazide], had a superior antifungal activity against both C. auris and C. albicans. Both SPB00525 and HTS06170 act as antivirulence agents and inhibited the invasive hyphal growth and biofilm formation of C. albicans. SPB00525 and HTS06170 attenuated fungal damage to human enterocytes and ameliorate the survival of Galleria mellonella larvae used as systemic candidiasis model. These data suggest that inhibiting fungal Δ(9) fatty acid desaturase activity represents a potential therapeutic approach for treating fungal infection caused by the superbug C. auris and the most prevalent human fungal pathogen, C. albicans.
Asunto(s)
Antifúngicos , Candida auris , Candidiasis , Pruebas de Sensibilidad Microbiana , Antifúngicos/farmacología , Animales , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Candida auris/efectos de los fármacos , Candida auris/genética , Ácido Graso Desaturasas/metabolismo , Ácido Graso Desaturasas/genética , Ácido Graso Desaturasas/antagonistas & inhibidores , Candida albicans/efectos de los fármacos , Candida albicans/enzimología , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Humanos , Inhibidores Enzimáticos/farmacología , Mariposas Nocturnas/microbiología , Mariposas Nocturnas/efectos de los fármacos , Metabolómica , Larva/microbiología , Larva/efectos de los fármacos , Modelos Animales de Enfermedad , Hidrazinas/farmacología , Bibliotecas de Moléculas Pequeñas/farmacología , Perfilación de la Expresión GénicaRESUMEN
The emergence of the "super fungus" Candida auris poses a significant threat to human health, given its multidrug resistance and high mortality rates. Therefore, developing a new antifungal strategy is necessary. Our previous research showed that Baicalein (BE), a key bioactive compound from the dried root of the perennial herb Scutellaria baicalensis Georgi, has strong fungistatic properties against C. auris. Nevertheless, the antifungal activity of BE against C. auris and its mechanism of action requires further investigation. In this study, we explored how BE affects this fungus using various techniques, including scanning electron microscopy (SEM), Annexin V-FITC apoptosis detection, CaspACE FITC-VAD-FMK In Situ Marker, reactive oxygen species (ROS) assay, singlet oxygen sensor green (SOSG) fluorescent probe, enhanced mitochondrial membrane potential (MMP) assay with JC-1, DAPI staining, TUNEL assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Our findings revealed that BE induced several apoptotic features, including phosphatidylserine (PS) externalization, metacaspase activation, nuclear condensation and DNA fragmentation. BE also increased intracellular ROS levels and altered mitochondrial functions. Additionally, transcriptomic analysis and RT-qPCR validation indicated that BE may induce apoptosis in C. auris by affecting ribosome-related pathways, suggesting that ribosomes could be new targets for antifungal agents, in addition to cell walls, membranes, and DNA. This study emphasizes the antifungal activity and mechanism of BE against C. auris, offering a promising treatment strategy for C. auris infection.
Asunto(s)
Antifúngicos , Apoptosis , Candida , Flavanonas , Potencial de la Membrana Mitocondrial , Especies Reactivas de Oxígeno , Ribosomas , Flavanonas/farmacología , Apoptosis/efectos de los fármacos , Candida/efectos de los fármacos , Antifúngicos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ribosomas/efectos de los fármacos , Ribosomas/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Fragmentación del ADN/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , HumanosRESUMEN
BACKGROUND: Sophorolipids are glycolipid biosurfactants with potential antibacterial, antifungal, and anticancer applications, rendering them promising for research. Therefore, this study hypothesizes that sophorolipids may have a notable impact on disrupting membrane integrity and triggering the production of reactive oxygen species, ultimately resulting in the eradication of pathogenic microbes. RESULTS: The current study resulted in the isolation of two Metschnikowia novel yeast strains. Sophorolipids production from these strains reached maximum yields of 23.24 g/l and 21.75 g/l, respectively, at the bioreactors level. Biosurfactants sophorolipids were characterized using FTIR and LC-MS techniques and found to be a mixture of acidic and lactonic forms with molecular weights of m/z 678 and 700. Our research elucidated sophorolipids' mechanism in disrupting bacterial and fungal membranes through ROS generation, confirmed by transmission electron microscopy and FACS analysis. The results showed that these compounds disrupted the membrane integrity and induced ROS production, leading to cell death in Klebsiella pneumoniae and Fusarium solani. In addition, the anticancer properties of sophorolipids were investigated on the A549 lung cancer cell line and found that sophorolipid-11D (SL-11D) and sophorolipid-11X (SL-11X) disrupted the actin cytoskeleton, as evidenced by immunofluorescence microscopy. The A549 cells were stained with Acridine orange/Ethidium bromide, which showed that they underwent necrosis. This was confirmed by flow cytometric analysis using Annexin/PI staining. The SL-11D and SL-11X molecules exhibited low levels of haemolytic activity and in-vitro cytotoxicity in HEK293, Caco-2, and L929 cell lines. CONCLUSION: In this work, novel yeast species CIG-11DT and CIG-11XT, isolated from the bee's gut, produce significant yields of sophorolipids without needing secondary oil sources, indicating a more economical production method. Our research shows that sophorolipids disrupt bacterial and fungal membranes via ROS production. They suggest they may act as chemo-preventive agents by inducing apoptosis in lung cancer cells, offering the potential for enhancing anticancer therapies.
Asunto(s)
Antifúngicos , Antineoplásicos , Metschnikowia , Estrés Oxidativo , Especies Reactivas de Oxígeno , Tensoactivos , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/metabolismo , Humanos , Tensoactivos/farmacología , Tensoactivos/metabolismo , Tensoactivos/química , Estrés Oxidativo/efectos de los fármacos , Antineoplásicos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Células A549 , Metschnikowia/metabolismo , Metschnikowia/efectos de los fármacos , Fusarium/efectos de los fármacos , Fusarium/metabolismo , Klebsiella pneumoniae/efectos de los fármacos , Glucolípidos/farmacología , Glucolípidos/metabolismo , Pruebas de Sensibilidad Microbiana , Ácidos OléicosRESUMEN
Background: Pythium insidiosum (P. insidiosum) is the causative agent of pythiosis, an infectious disease with a high morbidity and fatality rate. Pythiosis cases have increased dramatically during the past ten years, particularly in tropical and subtropical areas. Sadly, microbiologists and medical professionals know very little about pythiosis, and the disease is frequently challenging to identify. It is frequently misdiagnosed as a fungal infection. Methods: We report two cases of pythiosis, one was Pythium keratitis, the other was cutaneous pythiosis. The patient with corneal infection had no underlying disease, while the patient with cutaneous pythiosis had a history of liver cirrhosis, diabetes, and psoriasis. The corneal sample and subcutaneous pus were sent for metagenomic Next-Generation Sequencing (mNGS). To further diagnose the isolated strain, P. insidiosum zoospores were induced to produce by co-incubation with sterile grass leaves in sterile pond water. Their zoospores were used as an inoculum for drug susceptibility testing by disk diffusion and broth microdilution method. Results: The mNGS of two cases were reported as P. insidiosum. Zoospores were produced after incubation 48h. The zoospores were collected for drug susceptibility assay. All antifungal drugs, antibacterial drugs of ß-Lactams, vancomycin, levofloxacin, ciprofloxacin, gentamicin, trimethoprim-sulfamethoxazole, clindamycin have no inhibitory activity against P. insidiosum in vitro. Minocycline, tigecycline, linezolid, erythromycin and azithromycin have significant in vitro activity against P. insidiosum. Based on the susceptibility results, the drug was changed from itraconazole to linezolid and minocycline, along with multiple debridements and drainage for cutaneous pythiosis. The patient was discharged after 24 days of treatment. Conclusions: Early and accurate identification, combined with aggressive surgical debridement and appropriate drug therapy, can greatly improve patient managements. Conventional culture and zoospore induction remain gold standard for diagnosis; however, DNA-based method should be performed simultaneously. The drug susceptibility testing provides profound effects on proper drug selection against P. insidiosum.
Asunto(s)
Antifúngicos , Pruebas de Sensibilidad Microbiana , Pitiosis , Pythium , Pythium/aislamiento & purificación , Pythium/efectos de los fármacos , Pythium/genética , Humanos , Pitiosis/diagnóstico , Pitiosis/microbiología , Pitiosis/tratamiento farmacológico , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Masculino , Errores Diagnósticos , Enfermedades Transmisibles Emergentes/microbiología , Enfermedades Transmisibles Emergentes/diagnóstico , Enfermedades Transmisibles Emergentes/tratamiento farmacológico , Queratitis/microbiología , Queratitis/diagnóstico , Queratitis/tratamiento farmacológico , Persona de Mediana Edad , Secuenciación de Nucleótidos de Alto Rendimiento , Femenino , AncianoRESUMEN
Background: In the face of increasing antifungal resistance among Candida albicans biofilms, this study explores the efficacy of a combined treatment using Kangbainian lotion (KBN) and miconazole nitrate (MN) to address this challenge. Methods: Using UPLC-Q-TOF/MS Analysis for Identification of Active Compounds in KBN Lotion; FICI for synergy evaluation, XTT and ROS assays for biofilm viability and oxidative stress, fluorescence and confocal laser scanning microscopy (CLSM) for structural and viability analysis, and real-time fluorescence for gene expression. Conclusion: Our study indicates that the combined application of KBN and MN somewhat impacts the structural integrity of Candida albicans biofilms and affects the expression of several key genes involved in biofilm formation, including ALS1, ALS3, HWP1, HSP90, and CSH1. These preliminary findings suggest that there may be a synergistic effect between KBN and MN, potentially influencing not only the structural aspects of fungal biofilms but also involving the modulation of genetic pathways during their formation.
Asunto(s)
Antifúngicos , Biopelículas , Candida albicans , Farmacorresistencia Fúngica , Sinergismo Farmacológico , Miconazol , Pruebas de Sensibilidad Microbiana , Biopelículas/efectos de los fármacos , Candida albicans/efectos de los fármacos , Antifúngicos/farmacología , Miconazol/farmacología , Especies Reactivas de Oxígeno/metabolismo , Viabilidad Microbiana/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , HumanosRESUMEN
Candida albicans is an opportunistic fungal pathogen that can cause systemic infections in immunocompromised individuals. Morphological transition and biofilm formation are major virulence factors of C. albicans. Moreover, biofilm enhances resistance to antifungal agents. Therefore, it is urgent to identify new and effective compounds to target the biofilm of C. albicans. In the present study, the antifungal activities of equol against C. albicans were investigated. In vitro, the microdilution analysis and spot assay result showed that equol exhibited potent inhibitory activities against C. albicans. Further investigations confirmed that the antifungal effects of equol involved interference with the transition from yeast to hypha and biofilm formation of C. albicans. In addition, transcriptome sequencing and reverse transcription-quantitative PCR (qRT-PCR) analysis showed that equol significantly downregulated the expression of several genes in the Ras1-cAMP-PKA pathway related to hyphae and biofilm formation and significantly upregulated the expression of the negative transcriptional repressors RFG1 and TUP1. Moreover, equol effectively reduced the production of cAMP, a key messenger in the Ras1-cAMP-PKA pathway, while supplementation with cAMP partly rescued the equol-induced defects in hyphal development. Furthermore, in a mouse model of systemic candidiasis (SC), equol treatment significantly decreased the fungal burden (liver, kidneys, and lung) in mice and local tissue damage, while enhancing the production of interleukin-10 (IL-10). Together, these findings confirm that equol is a potentially effective agent for treatment of SC.
Asunto(s)
Antifúngicos , Biopelículas , Candida albicans , Candidiasis , Equol , Candida albicans/efectos de los fármacos , Candida albicans/genética , Animales , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Ratones , Candidiasis/microbiología , Candidiasis/tratamiento farmacológico , Equol/farmacología , Femenino , Modelos Animales de Enfermedad , Pruebas de Sensibilidad Microbiana , Hifa/efectos de los fármacos , Hifa/crecimiento & desarrollo , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Ratones Endogámicos BALB C , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismoRESUMEN
BACKGROUND: Pseudomonas eucalypticola, a new species of the P. fluorescens group that generates most Pseudomonas-based biocontrol agents, has not been found in any plants other than Eucalyptus dunnii leaves. Except for antagonism to the growth of a few fungi, its features in plant growth promotion and disease control have not been evaluated. Here, we identified a similar species of P. eucalypticola, 1021Bp, from endophyte cultures of healthy leaves of English boxwood (Buxus sempervirens 'Suffruticosa') and investigated its antifungal activity, plant growth promotion traits, and potential for boxwood blight control. RESULTS: Colorimetric or plate assays showed the properties of 1021Bp in nitrogen fixation, phosphate solubilization, and production of indole-3-acetic acid (IAA) and siderophores, as well as the growth suppression of all five plant fungal pathogens, including causal agents of widespread plant diseases, gray mold, and anthracnose. Boxwood plant leaves received 87.4% and 65.8% protection from infection when sprayed with cell-free cultural supernatant (CFS) but not the resuspended bacterial cells at 108-9/mL of 1021Bp at one and seven days before inoculation (dbi) with boxwood blight pathogen, Calonectria pseudonaviculata, at 5 × 104 spores/mL. They also received similarly high protection with the 1021Bp cell culture without separation of cells and CFS at 14 dbi (67.5%), suggesting a key role of 1021Bp metabolites in disease control. CONCLUSIONS: Given the features of plant growth and health and its similarity to P. eucalypticola with the P. fluorescens lineage, 1021Bp has great potential to be developed as a safe and environmentally friendly biofungicide and biofertilizer. However, its metabolites are the major contributors to 1021Bp activity for plant growth and health. Application with the bacterial cells alone, especially with nonionic surfactants, may result in poor performance unless survival conditions are present.
Asunto(s)
Enfermedades de las Plantas , Hojas de la Planta , Pseudomonas , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Pseudomonas/genética , Pseudomonas/crecimiento & desarrollo , Pseudomonas/metabolismo , Hojas de la Planta/microbiología , Antibiosis , Ácidos Indolacéticos/metabolismo , Hongos/crecimiento & desarrollo , Hongos/genética , Hongos/clasificación , Hongos/efectos de los fármacos , Sideróforos/metabolismo , Endófitos/metabolismo , Endófitos/genética , Desarrollo de la Planta , Agentes de Control Biológico , Antifúngicos/farmacología , Antifúngicos/metabolismoRESUMEN
Butterfly pea flower (Clitoria ternatea) may serve as an alternative anti-dandruff treatment; however, its effects on Malassezia spp. remain unexplored. The aim of this study was to explore the effects of C. ternatea as an herbal-based anti-dandruff treatment on Malassezia spp. DNA expression, plakoglobin levels, IL-8 levels, sebum levels, dandruff severity scores, adverse effects, and patient satisfaction. An experimental study with a pretest-posttest control design was conducted at the Outpatient Clinic of Dermatology and Venereology, Arifin Achmad Hospital, Pekanbaru, Indonesia, from November 2023 to January 2024. The flower of C. ternatea was used to formulate the shampoo. The study involved 70 female patients aged 18-25 with dandruff, who were divided into two groups: (a) experimental group using 20% C. ternatea shampoo and (b) control group using 2% ketoconazole shampoo. The present study found that 2% ketoconazole shampoo significantly reduced Malassezia spp. DNA expression compared to 20% C. ternatea shampooo (Clitoria ternatea: ΔCq=1.76±3.18; ketoconazole: ΔCq=3.77±2.90; p=0.008). No significant difference was observed in plakoglobin levels (C. ternatea: ΔCq=1.98±3.63; ketoconazole: ΔCq=2.50±2.36; p=0.427) or IL-8 levels (C. ternatea: ΔCq=3.46±4.00; ketoconazole: ΔCq=4.16 ± 3.62; p=0.459). C. ternatea significantly reduced sebum levels more than ketoconazole (C. ternatea: 1.16±0.98%; ketoconazole: 0.22±0.38%; p<0.001). Dandruff scores and patient satisfaction were similar for both shampoos (p=0.115 and p=0.336, respectively). Adverse effects were more common in the 2% ketoconazole shampoo group, affecting 21.2% of the patients. In conclusion, 2% ketoconazole shampoo is more effective in reducing Malassezia spp. DNA expression, while 20% C. ternatea shampoo offers better sebum control. Both shampoos are similarly effective in ameliorating dandruff severity and are well-tolerated, with fewer adverse effects reported for C. ternatea.
Asunto(s)
Caspa , Malassezia , Humanos , Femenino , Adulto , Caspa/tratamiento farmacológico , Caspa/microbiología , Malassezia/efectos de los fármacos , Preparaciones para el Cabello/farmacología , Adolescente , Adulto Joven , Cetoconazol/farmacología , Indonesia , Flores , Clitoria/química , Antifúngicos/farmacología , Satisfacción del PacienteRESUMEN
Silver nanoparticles (AgNPs) synthesized from plant extracts have gained attention for their potential applications in biomedicine. Calotropis gigantea has been utilized to synthesize AgNPs, called AgNPs-LCg, and exhibit antibacterial activities against both Gram-positive and Gram-negative bacteria as well as antifungal. However, further enhancement of their antimicrobial properties is needed. The aim of this study was to synthesize AgNPs-LCg and to enhance their antimicrobial and antifungal activities through a hybrid green synthesis reaction using patchouli oil (PO), as well as to characterize the synthesized AgNPs-LCg. Optimization was conducted using the response surface method (RSM) with a central composite design (CCD). AgNPs-LCg were synthesized under optimal conditions and hybridized with different forms of PO-crude, distillation wastewater (hydrolate), and heavy and light fractions-resulting in PO-AgNPs-LCg, PH-AgNPs-LCg, LP-AgNPs-LCg, and HP-AgNPs-LCg, respectively. The samples were then tested for their antibacterial (both Gram-positive and Gram-negative bacteria) and antifungal activities. Our data indicated that all samples, including those with distillation wastewater, had enhanced antimicrobial activity. HP-AgNPs-LCg, however, had the highest efficacy; therefore, only HP-AgNPs-LCg proceeded to the characterization stage for comparison with AgNPs-LCg. UV-Vis spectrophotometry indicated surface plasmon resonance (SPR) peaks at 400 nm for AgNPs-LCg and 360 nm for HP-AgNPs-LCg. The Fourier-transform infrared spectroscopy (FTIR) analysis confirmed the presence of O-H, N-H, and C-H groups in C. gigantea extract and AgNP samples. The smallest AgNPs-LCg were 56 nm, indicating successful RSM optimization. Scanning electron microscopy (SEM) analysis revealed spherical AgNPs-LCg and primarily cubic HP-AgNPs-LCg, with energy-dispersive X-ray spectroscopy (EDX) confirming silver's predominance. This study demonstrated that PO in any form significantly enhances the antimicrobial properties of AgNPs-LCg. The findings pave the way for the exploration of enhanced and environmentally sustainable antimicrobial agents, capitalizing on the natural resources found in Aceh Province, Indonesia.
Asunto(s)
Calotropis , Tecnología Química Verde , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Hojas de la Planta , Plata , Nanopartículas del Metal/química , Plata/química , Plata/farmacología , Tecnología Química Verde/métodos , Hojas de la Planta/química , Calotropis/química , Bacterias Grampositivas/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Aceites de Plantas/farmacología , Aceites de Plantas/químicaRESUMEN
Systemic infection with Candida albicans poses a significant risk for people with weakened immune systems and carries a mortality rate of up to 60%. However, current therapeutic options have several limitations, including increasing drug tolerance, notable off-target effects, and severe adverse reactions. Over the past four decades, the progress in developing drugs to treat Candida albicans infections has been sluggish. This comprehensive review addresses the limitations of existing drugs and summarizes the efforts made toward redesigning and innovating existing or novel drugs through nanotechnology. The discussion explores the potential applications of nanomedicine in Candida albicans infections from four perspectives: nano-preparations for anti-biofilm therapy, innovative formulations of "old drugs" targeting the cell membrane and cell wall, reverse drug resistance therapy targeting subcellular organelles, and virulence deprivation therapy leveraging the unique polymorphism of Candida albicans. These therapeutic approaches are promising to address the above challenges and enhance the efficiency of drug development for Candida albicans infections. By harnessing nano-preparation technology to transform existing and preclinical drugs, novel therapeutic targets will be uncovered, providing effective solutions and broader horizons to improve patient survival rates.
Asunto(s)
Antifúngicos , Candida albicans , Candidiasis , Nanotecnología , Humanos , Candida albicans/efectos de los fármacos , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Candidiasis/tratamiento farmacológico , Nanotecnología/métodos , Animales , Farmacorresistencia Fúngica/efectos de los fármacos , Biopelículas/efectos de los fármacos , Nanomedicina/métodos , Nanopartículas/química , Nanopartículas/uso terapéutico , Sistemas de Liberación de Medicamentos/métodosRESUMEN
The natural terpenoid citral has antifungal activity against multiple fungi, but its bioactivity against oomycetes is unclear. Therefore, this study investigated the antioomycete activity and mechanism of citral against Phytophthora capsici, a highly destructive invasive oomycete. Results showed that citral not only had a great inhibition on the mycelial growth of P. capsici (EC50 = 94.15 mg/L), but also had a significant inhibition on multiple spores, such as sporangia formation, zoospore discharge and zoospore germination. Citral at 4000 mg/L exhibited favorable protective (73.33%) and curative efficacy (55.11%) against pepper Phytophthora blight. Citral significantly damaged the hyphal morphology, disrupted the cell membrane integrity, increased the permeability of cell membrane, and increased the glycerol content in P. capsici. A total of 250 upregulated and 288 downregulated proteins were identified in iTRAQ-based quantitative proteomic analysis. Downregulated proteins were mostly enriched in pathways of ABC transporters, cyanoamino acid metabolism and starch and sucrose metabolism, suggesting an inhibition of citral on transmembrane transporter (e.g., ABC transporters) and pathogenicity (e.g., ß-glucosidases) proteins. Upregulated proteins were enriched in biosynthesis of unsaturated fatty acids, pyruvate metabolism and glycolysis/gluconeogenesis, suggesting an activation of citral on energy generation proteins, including acyl-CoA oxidase, D-lactate dehydrogenase, pyruvate kinase, acetyl-CoA synthetase and phosphoenolpyruvate carboxykinase. Biochemical and iTRAQ analysis suggested that cell membrane may be the target of citral in P. capsici.