Biofilm-associated infections caused by Candida species present significant therapeutic challenges due to their resistance to conventional antifungal agents. This study compared the antifungal efficacy of trans-Cinnamaldehyde-a natural compound extracted and purified from Cinnamon Tra My (Vietnam)-with nystatin against Candida albicans, C. glabrata, and C. tropicalis in both planktonic and biofilm forms. Planktonic Minimum Inhibitory Concentration (PMIC) and Minimum Biofilm Inhibitory Concentration (MBIC) values were determined using the CLSI M27-A3 protocol and MTT assay, while biofilm structure was assessed via light microscopy. Nystatin demonstrated superior efficacy across all species, with MBIC100 values of 0.008 mg/mL for C. albicans and C. glabrata, and 0.032 mg/mL for C. tropicalis. In contrast, trans-Cinnamaldehyde required 0.32 mg/mL to achieve MBIC100 in C. albicans and C. glabrata, and 0.63 mg/mL in C. tropicalis. Microscopic analysis confirmed pronounced biofilm disruption in C. albicans post-treatment with trans-Cinnamaldehyde, whereas C. tropicalis biofilms remained structurally resilient. These findings highlight the species-dependent susceptibility of Candida biofilms and underscore nystatin's continued role as a frontline antifungal. Trans-Cinnamaldehyde, while less potent, shows promise as a natural adjunct, particularly against C. albicans and C. glabrata biofilms.

• Klíčová slova
• Antifungal resistance, Biofilm susceptibility, Candida biofilm, MBIC, Nystatin, PMIC, Structural analysis, trans-Cinnamaldehyde,
• MeSH
• akrolein * analogy a deriváty   farmakologie   chemie   MeSH
• antifungální látky * farmakologie   MeSH
• biofilmy * účinky léků   růst a vývoj   MeSH
• Candida albicans účinky léků   MeSH
• Candida glabrata účinky léků   MeSH
• Candida tropicalis účinky léků   MeSH
• Candida * účinky léků   fyziologie   MeSH
• mikrobiální testy citlivosti MeSH
• nystatin * farmakologie   MeSH
• rostlinné extrakty farmakologie   MeSH
• skořicovník ceylonský chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• akrolein * MeSH
• antifungální látky * MeSH
• cinnamaldehyde MeSH Prohlížeč
• nystatin * MeSH
• rostlinné extrakty MeSH

Antibiotic resistance is one of the biggest threats to global health. Fungal endophytes are important sources of active natural products with antimicrobial potential. The purpose of this study was to characterize the endophytes coexisting with Helichrysum oocephalum, evaluate their antimicrobial activities, and annotate the endophytes metabolites. Six fungal species, including Fusarium avenaceum and Fusarium tricinctum, were identified. Endophytes were cultured, and their metabolites were extracted. The antimicrobial effects of the extracts were tested against Staphylococcus aureus, Bacillus cereus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. In addition, anti-biofilm effects of the extracts were examined against P. aeruginosa and S. epidermidis. The metabolites in the most active extract were annotated on the basis of the LC-ESI-QToF-MS/MS data. In anti-biofilm studies, F. avenaceum extract was effective in destroying and inhibiting the biofilm formation of S. epidermidis. LC-MS analysis showed that most of the identified compounds in the active extracts were enniatins (cyclic hexadepsipeptides). However, apicidin derivatives were also annotated. Our results revealed that these endophytes, especially Fusarium species, have antimicrobial activity against S. aureus, B. cereus, and C. albicans and anti-biofilm activity against S. epidermidis. According to the literature, the observed antimicrobial activity can be attributed to the enniatins. However, further phytochemical and pharmacological studies are necessary in this regard.

• Klíčová slova
• Fusarium, LC–MS, antimicrobial, anti‐biofilm, endophyte, enniatin,
• MeSH
• antibakteriální látky * farmakologie   izolace a purifikace   chemie   MeSH
• antifungální látky * farmakologie   izolace a purifikace   chemie   MeSH
• antiinfekční látky * farmakologie   izolace a purifikace   chemie   MeSH
• Bacillus cereus účinky léků   MeSH
• biofilmy účinky léků   MeSH
• Candida albicans účinky léků   MeSH
• endofyty * chemie   metabolismus   izolace a purifikace   MeSH
• Escherichia coli účinky léků   MeSH
• Fusarium * chemie   metabolismus   MeSH
• mikrobiální testy citlivosti MeSH
• Pseudomonas aeruginosa účinky léků   MeSH
• Staphylococcus aureus účinky léků   MeSH
• Staphylococcus epidermidis účinky léků   MeSH
• tandemová hmotnostní spektrometrie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• antifungální látky * MeSH
• antiinfekční látky * MeSH

The ERG6 gene is crucial for the biosynthesis of ergosterol, a key component of yeast cell membranes. Our study examines the impact of ERG6 gene deletion on the membrane composition and physicochemical properties of the pathogenic yeast Candida glabrata. Specifically, we investigated changes in selected sterol content, phospholipid composition, transmembrane potential, and PDR16 gene activity. Sterol levels were measured using high-performance liquid chromatography, the phospholipid profile was analysed via thin-layer chromatography, transmembrane potential was assessed with fluorescence spectroscopy, and gene expression levels were determined by quantitative PCR. Our findings revealed a depletion of ergosterol, increased zymosterol and eburicol content, an increased phosphatidylcholine and a reduced phosphatidylethanolamine content in the Δerg6 strain compared to the wt. Additionally, the Δerg6 strain exhibited membrane hyperpolarization without changes in PDR16 expression. Furthermore, the Δerg6 strain showed increased sensitivity to the antifungals myriocin and aureobasidine A. These results suggest that ERG6 gene deletion leads to significant alterations in membrane composition and may activates an alternative ergosterol synthesis pathway in the C. glabrata Δerg6 deletion mutant.

• Klíčová slova
• Candida glabrata, ERG6, Eburicol, Ergosterol, Phospholipids, Transmembrane potential,
• MeSH
• antifungální látky farmakologie   MeSH
• buněčná membrána * metabolismus   chemie   účinky léků   MeSH
• Candida glabrata * genetika   metabolismus   účinky léků   cytologie   MeSH
• delece genu * MeSH
• ergosterol metabolismus   biosyntéza   MeSH
• fosfolipidy metabolismus   MeSH
• fungální proteiny * genetika   metabolismus   MeSH
• membránové potenciály účinky léků   MeSH
• regulace genové exprese u hub MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antifungální látky MeSH
• ergosterol MeSH
• fosfolipidy MeSH
• fungální proteiny * MeSH

The present study has undertaken the isolation of marine yeasts from mangrove sediment samples and their ability to produce alkaline protease enzymes. A total of 14 yeast isolates were recovered on yeast-malt agar (YMA) and yeast extract peptone dextrose (YEPD) agar medium. After screening for proteolytic activity on skim milk agar, marine yeast isolate, AKB-1 exhibited a hydrolysis zone of 18 mm. Optimal conditions for the enzyme production from yeast isolate AKB-1 were at 30 °C, pH 8, fructose as carbon source, potassium nitrate as nitrogen source, and 25% saline concentration. Under the optimal conditions, the protease enzyme activity of the isolate AKB-1 was observed to be 978 IU/mL. The structural and functional analysis was carried out through FTIR and HPLC analysis for the extracted protease enzyme. Furthermore, the enzyme produced was partially purified by solvent extraction using ethyl acetate and ammonium sulfate precipitation (3.4-fold) followed by dialysis (56.8-fold). The molecular weight of the purified enzyme was observed to be around 60 kDa using SDS-PAGE. The extracted protein showed good antibacterial activity against six different clinical bacterial pathogens and the highest against Bacillus cereus (16 ± 0.5 mm). The extracted protease enzyme was revealed to remove blood stains from cloth within 20 min of application similar to the commercial detergent. The marine yeast isolate was further identified as Candida orthopsilosis AKB-1 (Accession number KY348766) through 18S rRNA sequencing, and a phylogenetic tree was generated.

• Klíčová slova
• Antibacterial, FTIR, HPLC, Mangrove sediment, Marine yeast, Protease enzyme,
• MeSH
• antibakteriální látky farmakologie   metabolismus   chemie   izolace a purifikace   MeSH
• Bacillus cereus účinky léků   MeSH
• bakteriální proteiny * chemie   farmakologie   metabolismus   izolace a purifikace   MeSH
• Candida * enzymologie   izolace a purifikace   genetika   klasifikace   MeSH
• endopeptidasy * chemie   metabolismus   izolace a purifikace   farmakologie   MeSH
• fylogeneze MeSH
• geologické sedimenty mikrobiologie   MeSH
• koncentrace vodíkových iontů MeSH
• kultivační média chemie   MeSH
• mikrobiální testy citlivosti MeSH
• molekulová hmotnost MeSH
• stabilita enzymů MeSH
• teplota MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkaline protease MeSH Prohlížeč
• antibakteriální látky MeSH
• bakteriální proteiny * MeSH
• endopeptidasy * MeSH
• kultivační média MeSH

Natural killer (NK) cells are critical components of the innate immune system. Their primary role is to induce apoptosis in target cells, such as cancerous or virally infected cells. These targets are recognized through interactions between activating or inhibitory receptors on the NK cell surface. Among the activating receptors is the natural cytotoxicity receptor NKp46. Several ligands for this receptor have been identified, including the epithelial adhesin Epa1 from the yeast Candida glabrata. Invasive candidiasis caused by this yeast is a significant complication for patients with hematological diseases. The interaction between NKp46 and Epa1 is thought to depend specifically on an O-glycan at threonine 225 of NKp46. To elucidate the molecular details of this interaction, we optimized the recombinant production of soluble NKp46 and Epa1, generated glycosylation variants of multiple NKp46 mutants, and evaluated the role of NKp46 glycosylation in Epa1 binding using microscale thermophoresis and isothermal titration calorimetry. Additionally, for the first time, we provide a comprehensive glycosylation profile of NKp46, determined through mass spectrometry of intact glycopeptides obtained by O-glycoprotease and trypsin proteolysis. Our findings demonstrate that the NKp46 stalk is glycosylated at multiple sites, involving both an N-glycan and more than one O-glycan. These glycans are critical for the interaction with Epa1, providing NK cells with enhanced sensitivity to Candida glabrata epitopes.

• Klíčová slova
• Adhesin, Candida glabrata, Epa1, N-glycosylation, NK cells, NKp46, O-glycosylation,
• MeSH
• antigeny Ly * metabolismus   chemie   MeSH
• buňky NK * imunologie   metabolismus   MeSH
• Candida glabrata * metabolismus   MeSH
• fungální proteiny * metabolismus   chemie   MeSH
• glykosylace MeSH
• lidé MeSH
• receptor 1 spouštějící přirozenou cytotoxicitu * metabolismus   chemie   genetika   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny Ly * MeSH
• epithelial adhesin 1, Candida glabrata MeSH Prohlížeč
• fungální proteiny * MeSH
• lektiny MeSH
• NCR1 protein, human MeSH Prohlížeč
• receptor 1 spouštějící přirozenou cytotoxicitu * MeSH

Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals. Although mucocutaneous candidiasis is generally not life-threatening, it can cause considerable discomfort, recurrent infections, and complications, particularly in patients with underlying conditions such as diabetes or in those taking immunosuppressive therapies. The rise of difficult-to-treat Candida infections is driven by new host factors and antifungal resistance. Pathogens, such as Candida auris (Candidozyma auris) and fluconazole-resistant Candida parapsilosis, pose serious global health risks. Recent taxonomic revisions have reclassified several Candida spp, potentially causing confusion in clinical practice. Current management guidelines are limited in scope, with poor coverage of emerging pathogens and new treatment options. In this Review, we provide updated recommendations for managing Candida infections, with detailed evidence summaries available in the appendix.

• MeSH
• antifungální látky * terapeutické užití   MeSH
• Candida klasifikace   účinky léků   izolace a purifikace   MeSH
• celosvětové zdraví MeSH
• fungální léková rezistence MeSH
• kandidóza * diagnóza   farmakoterapie   mikrobiologie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antifungální látky * MeSH

BACKGROUND: Antimicrobial lock therapy is recommended for preventing and treating catheter-related bloodstream infections, but different solutions have uncertain efficacy. METHODS: Two locks, 1.35% taurolidine and 4% ethylenediaminetetraacetic acid (EDTA), were tested on Staphylococcus epidermidis, Staphylococcus aureus, methicillin-resistant S. aureus, Pseudomonas aeruginosa, multidrug-resistant P. aeruginosa, vancomycin-resistant Enterococcus faecium, Klebsiella oxytoca (carbapenemase producing), K. pneumoniae (extended-spectrum β-lactamase producing), Candida albicans, and Candida glabrata. Broviac catheter segments were incubated with these organisms and then exposed to various lock solutions. Colony-forming units (CFUs) were counted after 2, 4, and 24 h of incubation. RESULTS: Taurolidine showed a significant decrease in CFUs after 2 h in S. aureus, S. epidermidis, methicillin-resistant S. aureus, vancomycin-resistant E. faecium, P. aeruginosa (both sensitive and multidrug-resistant strains), K. oxytoca, C. albicans, and C. glabrata. After 4 h, significant reductions were noted in S. aureus, S. epidermidis, methicillin-resistant S. aureus, P. aeruginosa, multidrug-resistant P. aeruginosa, K. pneumoniae, K. oxytoca, and C. albicans. Taurolidine was also effective after 24 h, especially against methicillin-resistant S. aureus and multidrug-resistant P. aeruginosa. Four percent EDTA acid showed a significant reduction in CFUs after 2 h in S. aureus, vancomycin-resistant E. faecium, P. aeruginosa, K. oxytoca, C. albicans, and C. glabrata. After 4 h, reductions occurred in P. aeruginosa, multidrug-resistant P. aeruginosa, K. oxytoca, and C. albicans and after 24 h in methicillin-resistant S. aureus, P. aeruginosa, and K. oxytoca. CONCLUSION: Taurolidine is more effective than 4% EDTA acid in eradicating Gram-positive and Gram-negative microorganisms and fungi.

• Klíčová slova
• antimicrobial lock, catheter‐related blood stream infection, ethylenediaminetetraacetic acid, home parenteral nutrition, taurolidine, venous catheter,
• MeSH
• antiinfekční látky * farmakologie   MeSH
• Candida albicans účinky léků   MeSH
• EDTA * farmakologie   MeSH
• katétrové infekce * prevence a kontrola   mikrobiologie   MeSH
• lidé MeSH
• methicilin rezistentní Staphylococcus aureus účinky léků   MeSH
• mikrobiální testy citlivosti MeSH
• počet mikrobiálních kolonií MeSH
• Pseudomonas aeruginosa účinky léků   MeSH
• Staphylococcus aureus účinky léků   MeSH
• Staphylococcus epidermidis účinky léků   MeSH
• taurin * analogy a deriváty   farmakologie   MeSH
• thiadiaziny * farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• antiinfekční látky * MeSH
• EDTA * MeSH
• taurin * MeSH
• taurolidine MeSH Prohlížeč
• thiadiaziny * MeSH

The opportunistic pathogen Candida parapsilosis is a major causative agent of candidiasis leading to death in immunocompromised individuals. Azoles are the first line of defense in their treatment. The purpose of this study was to characterize eight fluconazole-resistant and sensitive C. parapsilosis hospital isolates through a battery of phenotypic tests that target pathogenicity attributes such as virulence, biofilm formation, stress resistance, and ergosterol content. Whole genome sequencing was carried out to identify mutations in key pathogenicity and resistance genes. Phylogenetic comparison was performed to determine strain relatedness and clonality. Genomic data and phylogenetic analysis revealed that two isolates were C. orthopsilosis and C. metapsilosis misidentified as C. parapsilosis. Whole genome sequencing analysis revealed known and novel mutations in key drug resistance and pathogenicity genes such as ALS6, ALS7, SAPP3, SAP7, SAP9, CDR1, ERG6, ERG11 and UPC2. Phylogenetic analysis revealed a high degree of relatedness and clonality within our C. parapsilosis isolates. Our results showed that resistant isolates exhibited an increase in biofilm content compared to the sensitive isolates. In conclusion, our study is the first of its kind in Lebanon to describe phenotypic and genotypic characteristics of nosocomial C. parapsilosis complex isolates having a remarkable ability to form biofilms.

• Klíčová slova
• Candida parapsilosis, Biofilm, Clonality, Fluconazole, Pathogenicity, Resistance,
• MeSH
• antifungální látky farmakologie   MeSH
• biofilmy růst a vývoj   účinky léků   MeSH
• Candida parapsilosis * genetika   izolace a purifikace   účinky léků   klasifikace   patogenita   MeSH
• fenotyp MeSH
• flukonazol farmakologie   MeSH
• fungální léková rezistence genetika   MeSH
• fylogeneze MeSH
• genotyp MeSH
• kandidóza * mikrobiologie   farmakoterapie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• mutace MeSH
• nemocnice MeSH
• sekvenování celého genomu MeSH
• virulence genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Libanon MeSH
• Názvy látek
• antifungální látky MeSH
• flukonazol MeSH

Amphotericin B (AmB) is one of the most effective antifungal drugs, with a strong, dose-dependent activity against most Candida and Aspergillus species responsible for life-threatening infections. However, AmB is severely toxic, which hinders its broad use. In this proof-of-concept study, we demonstrate that prodrugging AmB considerably decreases AmB toxicity without affecting its fungicidal activity. For this purpose, we modified the AmB structure by attaching a designer phosphate promoiety, thereby switching off its mode of action and preventing its toxic effects. The original fungicidal activity of AmB was then restored upon prodrug activation by host plasma enzymes. These AmB prodrugs showed a safer toxicity profile than commercial AmB deoxycholate in Candida and Aspergillus species and significantly prolonged larval survival of infected Galleria mellonella larvae. Based on these findings, prodrugging toxic antifungals may be a viable strategy for broadening the antifungal arsenal, opening up opportunities for targeted prodrug design.

• Klíčová slova
• Amphotericin, Antifungal, Aspergillus fumigatus, Candida albicans, Fungal infection, Galleria mellonella, Prodrugs, Toxicity,
• MeSH
• amfotericin B * farmakologie   MeSH
• antifungální látky * farmakologie   chemie   chemická syntéza   MeSH
• Aspergillus účinky léků   MeSH
• Candida účinky léků   MeSH
• larva účinky léků   MeSH
• mikrobiální testy citlivosti * MeSH
• molekulární struktura MeSH
• můry účinky léků   MeSH
• prekurzory léčiv * farmakologie   chemie   chemická syntéza   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amfotericin B * MeSH
• antifungální látky * MeSH
• prekurzory léčiv * MeSH

Polymicrobial biofilms, the reason for most chronic wound infections, play a significant role in increasing antibiotic resistance. The in vivo effectiveness of the new anti-biofilm therapy is conditioned by the profound evaluation using appropriate in vitro biofilm models. Since nutrient availability is crucial for in vitro biofilm formation, this study is focused on the impact of four selected cultivation media on the properties of methicillin-resistant Staphylococcus aureus and Candida albicans dual-species biofilms. To reflect the wound environment, Tryptic soy broth, RPMI 1640 with and without glucose, and Lubbock medium were supplemented with different amounts of host effector molecules present in human plasma or sheep red blood cells. The study demonstrates that the Lubbock medium provided the most appropriate amount of nutrients regarding the biomass structure and the highest degree of tolerance to selected antimicrobials with the evident contribution of the biofilm matrix. Our results allow the rational employment of nutrition conditions within methicillin-resistant Staphylococcus aureus and Candida albicans dual-species biofilm formation in vitro for preclinical research. Additionally, one of the potential targets of a complex antibiofilm strategy, carbohydrates, was revealed since they are prevailing molecules in the matrices regardless of the cultivation media.

• MeSH
• antibakteriální látky farmakologie   MeSH
• biofilmy * účinky léků   růst a vývoj   MeSH
• Candida albicans * účinky léků   fyziologie   MeSH
• kultivační média * farmakologie   MeSH
• lidé MeSH
• methicilin rezistentní Staphylococcus aureus * účinky léků   fyziologie   MeSH
• mikrobiální testy citlivosti MeSH
• ovce MeSH
• živiny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• kultivační média * MeSH