Candida haemulonii complex (Candida haemulonii [I], Candida duobushaemulonii [II], and Candida haemulonii var. vulnera [III]) has become relevant in recent times, not so much because of a high incidence in human clinical sample cultures but because of its remarkable antifungal resistance. The objective of this study was to evaluate several methods for the identification of this uncommon species of Candida. Ten isolates of C. haemulonii were identified by biochemical and proteomic methods, and their antifungal susceptibility testing was performed by both commercial and reference methods. MALDI-TOF MS (Vitek MS and Vitek MS PRIME) and Vitek2 correctly identified these genera but API method did not. There was a good correlation between the commercial methods and the reference methods for the AST. In conclusion Vitek MS, Vitek MS PRIME, and Vitek2 systems, but not API32C, are reliable for identification of C. haemulonii complex. Furthermore, MALDI-TOF MS systems could identify to the subspecies level. Commercial methods for antifungal susceptibility testing are valid for the study of this species and confirm amphotericin B and to azole resistance.
Within a eukaryotic cell, both lipid homeostasis and faithful cell cycle progression are meticulously orchestrated. The fission yeast Schizosaccharomyces pombe provides a powerful platform to study the intricate regulatory mechanisms governing these fundamental processes. In S. pombe, the Cbf11 and Mga2 proteins are transcriptional activators of non-sterol lipid metabolism genes, with Cbf11 also known as a cell cycle regulator. Despite sharing a common set of target genes, little was known about their functional relationship. This study reveals that Cbf11 and Mga2 function together in the same regulatory pathway, critical for both lipid metabolism and mitotic fidelity. Deletion of either gene results in a similar array of defects, including slow growth, dysregulated lipid homeostasis, impaired cell cycle progression (cut phenotype), abnormal cell morphology, perturbed transcriptomic and proteomic profiles, and compromised response to the stressors camptothecin and thiabendazole. Remarkably, the double deletion mutant does not exhibit a more severe phenotype compared to the single mutants. In addition, ChIP-nexus analysis reveals that both Cbf11 and Mga2 bind to nearly identical positions within the promoter regions of target genes. Interestingly, Mga2 binding appears to be dependent on the presence of Cbf11 and Cbf11 likely acts as a tether to DNA, while Mga2 is needed to activate the target genes. In addition, the study explores the distribution of Cbf11 and Mga2 homologs across fungi. The presence of both Cbf11 and Mga2 homologs in Basidiomycota contrasts with Ascomycota, which mostly lack Cbf11 but retain Mga2. This suggests an evolutionary rewiring of the regulatory circuitry governing lipid metabolism and mitotic fidelity. In conclusion, this study offers compelling support for Cbf11 and Mga2 functioning jointly to regulate lipid metabolism and mitotic fidelity in fission yeast.
- MeSH
- metabolismus lipidů * genetika MeSH
- mitóza * genetika MeSH
- regulace genové exprese u hub * MeSH
- Schizosaccharomyces pombe - proteiny * genetika metabolismus MeSH
- Schizosaccharomyces * genetika metabolismus MeSH
- transkripční faktory genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
The current global scenario presents us with a growing increase in infections caused by fungi, referred to by specialists in the field as a "silent epidemic", aggravated by the limited pharmacological arsenal and increasing resistance to this therapy. For this reason, drug repositioning and therapeutic compound combinations are promising strategies to mitigate this serious problem. In this context, this study investigates the antifungal activity of the non-toxic, low-cost and widely available cationic polyelectrolyte Poly(diallyldimethylammonium chloride) (PDDA), in combination with different antifungal drugs: systemic (amphotericin B, AMB), topical (clioquinol, CLIO) and oral (nitroxoline, NTX). For each combination, different drug:PDDA ratios were tested and, through the broth microdilution technique, the minimum inhibitory concentration (MIC) of these drugs in the different ratios against clinically important Candida species strains was determined. Overall, PDDA combinations with the studied drugs demonstrated a significant increase in drug activity against most strains, reaching MIC reductions of up to 512 fold for the fluconazole resistant Candida krusei (Pichia kudriavzevii). In particular, the AMB-PDDA combination 1:99 was highly effective against AMB-resistant strains, demonstrating the excellent profile of PDDA as an adjuvant/association in novel antifungal formulations with outdated conventional drugs.
- MeSH
- amfotericin B farmakologie MeSH
- antifungální látky * farmakologie MeSH
- Candida * účinky léků MeSH
- fungální léková rezistence MeSH
- kandidóza mikrobiologie farmakoterapie MeSH
- kvartérní amoniové sloučeniny * farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti * MeSH
- Pichia MeSH
- polyelektrolyty farmakologie MeSH
- polyethyleny farmakologie chemie MeSH
- synergismus léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Calcineurin-nuclear factor of activated T cells (CN-NFAT) inhibitors are widely clinically used drugs for immunosuppression, but besides their required T cell response inhibition, they also undesirably affect innate immune cells. Disruption of innate immune cell function can explain the observed susceptibility of CN-NFAT inhibitor-treated patients to opportunistic fungal infections. Neutrophils play an essential role in innate immunity as a defense against pathogens; however, the effect of CN-NFAT inhibitors on neutrophil function was poorly described. Thus, we tested the response of human neutrophils to opportunistic fungal pathogens, namely Candida albicans and Aspergillus fumigatus, in the presence of CN-NFAT inhibitors. Here, we report that the NFAT pathway members were expressed in neutrophils and mediated part of the neutrophil response to pathogens. Upon pathogen exposure, neutrophils underwent profound transcriptomic changes with subsequent production of effector molecules. Importantly, genes and proteins involved in the regulation of the immune response and chemotaxis, including the chemokines CCL2, CCL3, and CCL4 were significantly upregulated. The presence of CN-NFAT inhibitors attenuated the expression of these chemokines and impaired the ability of neutrophils to chemoattract other immune cells. Our results amend knowledge about the impact of CN-NFAT inhibition in human neutrophils.
- MeSH
- Aspergillus fumigatus imunologie MeSH
- Candida albicans imunologie MeSH
- chemotaxe MeSH
- kalcineurin * metabolismus MeSH
- lidé MeSH
- mykózy imunologie MeSH
- neutrofily * imunologie metabolismus MeSH
- signální transdukce * MeSH
- transkripční faktory NFATC * metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Endophytic microbes are plant-associated microorganisms that reside in the interior tissue of plants without causing damage to the host plant. Endophytic microbes can boost the availability of nutrient for plant by using a variety of mechanisms such as fixing nitrogen, solubilizing phosphorus, potassium, and zinc, and producing siderophores, ammonia, hydrogen cyanide, and phytohormones that help plant for growth and protection against various abiotic and biotic stresses. The microbial endophytes have attained the mechanism of producing various hydrolytic enzymes such as cellulase, pectinase, xylanase, amylase, gelatinase, and bioactive compounds for plant growth promotion and protection. The efficient plant growth promoting endophytic microbes could be used as an alternative of chemical fertilizers for agro-environmental sustainability. Endophytic microbes belong to different phyla including Euryarchaeota, Ascomycota, Basidiomycota, Mucoromycota, Firmicutes, Proteobacteria, and Actinobacteria. The most pre-dominant group of bacteria belongs to Proteobacteria including α-, β-, γ-, and δ-Proteobacteria. The least diversity of the endophytic microbes have been revealed from Bacteroidetes, Deinococcus-Thermus, and Acidobacteria. Among reported genera, Achromobacter, Burkholderia, Bacillus, Enterobacter, Herbaspirillum, Pseudomonas, Pantoea, Rhizobium, and Streptomyces were dominant in most host plants. The present review deals with plant endophytic diversity, mechanisms of plant growth promotion, protection, and their role for agro-environmental sustainability. In the future, application of endophytic microbes have potential role in enhancement of crop productivity and maintaining the soil health in sustainable manner.
- MeSH
- Ascomycota * MeSH
- Bacillus * MeSH
- Bacteria genetika MeSH
- Basidiomycota * MeSH
- endofyty MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Laccase-producing fungus (MY3) was successfully isolated from soil samples collected from Mansoura Governorate, Egypt. This fungal isolate has shown a high laccase production level over other isolated fungi. The identity of this isolate was determined by the molecular technique 18SrRNA as Curvularia lunata MY3. The enzyme purification was performed using ammonium sulfate precipitation followed by Sephacryl S-200 and DEAE-Sepharose column chromatography. The denatured enzyme using SDS-PAGE had a molar mass of 65 kDa. The purified laccase had an optimum temperature at 40 °C for enzyme activity with 57.3 kJ/mol activation energy for 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) oxidation. The enzyme had an optimum pH of 5.0, and it has shown a high stability at the acidic range (4.5 to 5.5). Mn2+ and Mg2+ ions enhanced the enzyme activity, while most of the enzyme activity was inhibited by Hg2+. Some compounds such as 2-mercaptoethanol, L-cysteine, and sodium azide at a concentration of 10 mmol/L had shown a high suppression effect on the enzyme activity. The enzyme strongly oxidized ABTS and syringaldazine and moderately oxidized DMP and guaiacol. The antimicrobial activity of the purified enzyme towards three pathogenic strains (Escherichia coli ATCC-25922, Staphylococcus aureus NRRLB-767, and Candida albicans ATCC-10231) was evaluated for the potential use as an antimicrobial therapeutic enzyme.
The application of pulsed electric fields (PEFs) is becoming a promising tool for application in biotechnology, and the food industry. However, real-time monitoring of the efficiency of PEF treatment conditions is challenging, especially at the industrial scale and in continuous production conditions. To overcome this challenge, we have developed a straightforward setup capable of real-time detection of yeast biological autoluminescence (BAL) during pulsing. Saccharomyces cerevisiae culture was exposed to 8 pulses of 100 μs width with electric field strength magnitude 2-7 kV cm-1. To assess the sensitivity of our method in detecting yeast electroporation, we conducted a comparison with established methods including impedance measurements, propidium iodide uptake, cell growth assay, and fluorescence microscopy. Our results demonstrate that yeast electroporation can be instantaneously monitored during pulsing, making it highly suitable for industrial applications. Furthermore, the simplicity of our setup facilitates its integration into continuous liquid flow systems. Additionally, we have established quantitative indicators based on a thorough statistical analysis of the data that can be implemented through a dedicated machine interface, providing efficiency indicators for analysis.
- MeSH
- elektroporace * metody MeSH
- Saccharomyces cerevisiae * růst a vývoj MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- červená rýže,
- MeSH
- dyslipidemie * terapie MeSH
- fermentace * MeSH
- fytoterapie metody MeSH
- lidé MeSH
- lovastatin škodlivé účinky terapeutické užití MeSH
- Monascus MeSH
- označování výrobků MeSH
- potravní doplňky MeSH
- rýže (rod) * klasifikace MeSH
- Check Tag
- lidé MeSH
INTRODUCTION: Despite antifungal advancements, candidaemia still has a high mortality rate of up to 40%. The ECMM Candida III study in Europe investigated the changing epidemiology and outcomes of candidaemia for better understanding and management of these infections. METHODS: In this observational cohort study, participating hospitals enrolled the first ten consecutive adults with blood culture-proven candidemia. Collected data included patient demographics, risk factors, hospital stay duration (follow-up of 90 days), diagnostic procedures, causative Candida spp., management details, and outcome. Controls were included in a 1:1 fashion from the same hospitals. The matching process ensured similarity in age (10-year range), primary underlying disease, hospitalization in intensive care versus non-ICU ward, and major surgery within 2 weeks before candidemia between cases and controls. Overall and attributable mortality were described, and a survival probability for cases and controls was performed. RESULTS: One hundred seventy-one pairs consisting of patients with candidemia and matched controls from 28 institutions were included. In those with candidemia, overall mortality was 40.4%. Attributable mortality was 18.1% overall but differed between causative Candida species (7.7% for Candida albicans, 23.7% for Candida glabrata/Nakaseomyces glabratus, 7.7% for Candida parapsilosis and 63.6% for Candida tropicalis). Regarding risk factors, the presence of a central venous catheter, total parenteral nutrition and acute or chronic renal disease were significantly more common in cases versus controls. Duration of hospitalization, and especially that of ICU stay, was significantly longer in candidemia cases (20 (IQR 10-33) vs 15 days (IQR 7-28); p = 0.004). CONCLUSIONS: Although overall and attributable mortality in this subgroup analysis of matched case/control pairs remains high, the attributable mortality appears to have decreased in comparison to historical cohorts. This decrease may be driven by improved prognosis of Candida albicans and Candida parapsilosis candidemia; whereas candidemia due to other Candida spp. exhibits a much higher attributable mortality.
- MeSH
- antifungální látky terapeutické užití MeSH
- Candida * izolace a purifikace klasifikace MeSH
- dospělí MeSH
- kandidemie * mortalita mikrobiologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- Geografické názvy
- Evropa MeSH
The paper reports a low-cost handheld source of a cold air plasma intended for biomedical applications that can be made by anyone (detailed technical information and a step-by-step guide for creating the NTP source are provided). The plasma source employs a 1.4 W corona discharge in the needle-to-cone electrode configuration and is an extremely simple device, consisting basically of two electrodes and a cheap power supply. To achieve the best bactericidal effect, the plasma source has been optimized on Escherichia coli. The bactericidal ability of the plasma source was further tested on a wide range of microorganisms: Staphylococcus aureus as a representative of gram-positive bacteria, Pseudomonas aeruginosa as gram-negative bacteria, Candida albicans as yeasts, Trichophyton interdigitale as microfungi, and Deinococcus radiodurans as a representative of extremophilic bacteria resistant to many DNA-damaging agents, including ultraviolet and ionizing radiation. The testing showed that the plasma source inactivates all the microorganisms tested in several minutes (up to 105-107 CFU depending on a microorganism), proving its effectiveness against a wide spectrum of pathogens, in particular microfungi, yeasts, gram-positive and gram-negative bacteria. Studies of long-lived reactive species such as ozone, nitrogen oxides, hydrogen peroxide, nitrite, and nitrate revealed a strong correlation between ozone and the bactericidal effect, indicating that the bactericidal effect should generally be attributed to reactive oxygen species. This is the first comprehensive study of the bactericidal effect of a corona discharge in air and the formation of long-lived reactive species by the discharge, depending on both the interelectrode distance and the discharge current.
