Search Results (95)

The most prevalent growth of Candida cells is based on biofilm development, which causes the intensification of antifungal resistance against a large range of chemicals. Nanoparticles can be synthesized using green methods via various biological extracts and reducing agents to control Candida biofilms. This study aims to compare copper oxide nanoparticles (CuONPs) synthesized through chemical methods and those synthesized using Cinnamomum verum-based green methods against Candida infections and their biofilms isolated from Iraqi patients, with the potential to improve treatment outcomes. The physical and chemical properties of these nanoparticles were characterized using Fourier-transform infrared spectroscopy (FT-IR,) scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM) and X-ray diffraction (XRD). Four strains of Candida were isolated and characterized from Iraqi patients in Tikrit Hospital and selected based on their ability to form biofilm on polystyrene microplates. The activity of green-synthesized CuONPs using cinnamon extract was compared with both undoped and doped (Fe, Sn) chemically synthesized CuONPs. Four pathogenic Candida strains (Candida glabrata, Candida lusitaniae, Candida albicans, and Candida tropicalis) were isolated from Iraqi patients, demonstrating high biofilm formation capabilities. Chemically and green-synthesized CuONPs from Cinnamomum verum showed comparable significant antiplanktonic and antibiofilm activities against all strains. Doped CuONPs with iron or tin demonstrated lower minimum inhibitory concentration (MIC) values, indicating stronger antibacterial activity, but exhibited weaker anti-adhesive properties compared to other nanoparticles. The antiadhesive activity revealed that C. albicans strain seems to produce the most resistant biofilms while C. glabrata strain seems to be more resistant towards the doped CuONPs. Moreover, C. tropicalis was the most sensitive to all the CuONPs. Remarkably, at a concentration of 100 µg/mL, all CuONPs were effective in eradicating preformed biofilms by 47–66%. The findings suggest that CuONPs could be effective in controlling biofilm formation by Candida species resistant to treatment in healthcare settings. Full article

Cytokinins, plant hormones derived from adenine, are best known for regulating growth and stress responses in plants. Recent findings suggest they may also influence microbial viability, yet their direct antimicrobial potential remains underexplored. This study evaluates the antimicrobial activities of four natural cytokinins (iPA, B, K, and p-T) and their N⁹-ribosides (iPAR, BR, KR, and p-TR) against selected human pathogens. Using the broth microdilution method, we assessed their effects on Gram-positive and Gram-negative bacteria, as well as fungal strains. While Gram-negative species showed no susceptibility, all tested compounds exhibited bacteriostatic activity against Bacillus subtilis and Enterococcus faecalis. Most notably, kinetin (K) and kinetin riboside (KR) displayed strong antifungal activity against Candida albicans, with MIC values comparable to the reference drug nystatin. Molecular docking studies supported these findings by showing that K and KR form favorable interactions with two validated antifungal targets in Candida albicans: secreted aspartic proteinase 3 (SAP3) and dihydrofolate reductase (DHFR). This is, to our knowledge, the first report linking natural cytokinins to direct antifungal action against C. albicans supported by in silico evidence. These findings highlight the potential of K and KR as promising leads for the development of cytokinin-based antifungal agents. Full article

Candidiasis belongs to common fungal infections and is usually mild and self-limiting. However, in patients with immunodeficiencies, it can transform into invasive infections with high mortality. Long-term antifungal treatment can lead to the emergence of resistance. The problem is further complicated by the development of fungal biofilm resistant to conventional antimicrobials. Due to a limited choice of available antifungals, the development of novel active agents, such as antimicrobial peptides (AMPs), is highly desirable. Human cathelicidin LL-37 is an intensively studied AMP with a confirmed broad spectrum of antimicrobial activities. Due to the relatively high costs of production, the design of shorter analogs of LL-37 has been recommended. In this study, we synthesized a KR12 amide, KRIVQRIKDFLR-NH₂, and its 24 derivatives obtained by substitution with fatty acids. The compounds were tested for their antifungal potential. They exhibited activity against the Candida albicans, C. glabrata, C. tropicalis and C. lipolytica. Five compounds: C₁₀-KR12-NH₂, C₁₂-KR12-NH₂, C₁₄-KR12-NH₂, 2-butyloctanoic acid-KR12-NH₂, and 4-phenylbenzoic acid-KR12-NH₂ were highly active against planktonic cells. C₁₄-KR12-NH₂ demonstrated also activity against C. albicans biofilm cultured on polystyrene for 24, 48 and 72 h. Lipidation has proven to be an effective strategy for improving microbiological activity of the KR12-NH₂ peptide. Full article

The aim of this study was to develop a novel functional ingredient—goat’s skim milk enriched with Agrocybe aegerita (V. Brig.) Vizzini mushroom extract (ME/M)—using Central Composite Design (CCD). The optimized ME/M ingredient was evaluated for its physico-chemical, techno-functional, biological, and antimicrobial properties. Physico-chemical properties were analyzed using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy, Scanning Electron Microscopy (SEM), and Dynamic Light Scattering (DLS). The ingredient exhibited a polymodal particle size distribution and contained glucans, along with a newly formed polypeptide resulting from the selective cleavage of goat milk proteins. A 0.1% ME/M solution demonstrated good emulsifying and foaming properties. Additionally, ME/M showed strong antiproliferative effects on human cancer cell lines, particularly Caco-2 (colorectal) and MCF7 (breast) cancer cells. The ingredient also promoted HaCaT cell growth without cytotoxic effects, suggesting its safety and potential wound-healing properties. Furthermore, the addition of ME/M to HaCaT cells inoculated with Staphylococcus aureus resulted in reduced IL-6 levels compared to the control (without ME/M), indicating a dose-dependent anti-inflammatory effect. The optimized ME/M ingredient also exhibited antibacterial, antifungal, anticandidal, and antibiofilm activity in one-fourth of MIC. These findings suggest that the formulated ME/M ingredient has strong potential for use in the development of functional foods offering both desirable techno-functional properties and bioactive benefits. Full article

Candida species, normally part of the healthy human flora, can cause severe opportunistic infections when their population increases. This risk is even greater in immunocompromised individuals. Women using intrauterine contraceptive devices (IUDs) are at higher risk for IUD-associated vulvovaginal candidiasis (VVC) because the device provides a surface for biofilm formation. This biofilm formation allows the normal flora to become opportunistic pathogens, leading to symptoms of VVC such as hemorrhage, pelvic pain, inflammation, itching and discharge. VVC is often linked to IUD use, requiring the prompt removal of these devices for effective treatment. This study evaluated the activity of the arginine-rich peptide “protamine” against Candida albicans, Candida tropicalis and Candida krusei isolated from IUD users who had signs of VVC. The antimicrobial activity was measured using the agar disk diffusion and microbroth dilution methods to determine the minimum inhibitory concentration (MIC). The MIC values of protamine against C. albicans, C. tropicalis and C. krusei are 32 μg mL⁻¹, 64 μg mL⁻¹ and 256 μg mL⁻¹, respectively. The determined MIC of protamine was used for a biofilm inhibition assay by crystal violet staining. Protamine inhibited the biofilm formation of the VVC isolates, and its mechanisms were studied through scanning electron microscopy (SEM) and a reactive oxygen species (ROS) assay. The disruption of cell membranes and the induction of oxidative stress appear to be key mechanisms underlying its anti-candidal effects. The results from an in vitro assay support the potential use of protamine as an antibiofilm agent to coat IUDs in the future for protective purposes. Full article

Gold nanoparticles have been identified as a promising avenue for the development of drug carriers, particularly in the context of antimicrobial drug delivery, where limited solubility represents a significant challenge. The ability of gold nanoparticles to penetrate biofilms and disrupt fungal cell membranes makes them an effective tool to support antifungal therapy, especially against resistant strains. Gold nanoparticles also demonstrate synergistic effects with chemotherapeutics and can influence the release profile of the active substances. This study aimed to develop a topical hydrogel drug formulation containing itraconazole (ITZ), with the addition of gold nanoparticles, to enhance its therapeutic properties. Due to ITZ’s poor water solubility, three types of the gold nanoparticles (AuNPs) of different sizes were synthesized and subsequently coated with itraconazole. The resulting formulations were incorporated into carbopol gels and their ability to diffuse through semipermeable membranes was assessed. The findings demonstrated that the combination of gold nanoparticles and itraconazole elevated the diffusion coefficient to twice the level observed in gels without nanoparticles. Furthermore, the combined effect of gold nanoparticles and itraconazole against a reference Candida albicans strain was investigated. The combination of gold nanoparticles and itraconazole demonstrated a growth-inhibitory effect on this strain, indicating that this formulation could potentially be employed in the treatment of fungal infections. The study confirms that hydrogels with itraconazole and gold nanoparticles can be obtained, offering enhanced drug diffusion. Full article

Candida albicans is an emerging multidrug-resistant opportunistic pathogen that causes candidiasis, superficial infections on the mucosa, nails or skin, and life-threatening candidemia in deep tissue when disseminated through the bloodstream. Recently, there has been a sharp rise in resistant strains, posing a considerable clinical challenge for the treatment of candidiasis. There has been a resurged interest in the pharmacological properties of essential oils and their active components, for example, monoterpenes with alcohol (-OH) and aldehyde (-CHO) groups. Eugenol and citral have shown promising in vitro and in vivo activity against Candida species. Although there is substantial research on the efficacy of these essential oil components against C. albicans, a detailed knowledge of their mycological mechanisms is lacking. To explore the broad-spectrum effects of EOs, it is more meaningful and rational to study the whole essential oil, along with some of its major components. This review provides a comprehensive overview of eugenol and citral anticandidal and antivirulence activity, alone and together, along with the associated mechanisms and limitations of our current knowledge. Full article

Tidal wetlands, commonly known as salt marshes, are highly productive ecosystems in temperate regions worldwide. These environments constitute a unique flora composed primarily of salt-tolerant herbs, grasses, and shrubs. This study investigated the therapeutic properties of ten salt marsh plants collected mainly from Palk Bay and Mannar Gulf against Candida disease. This study examined the changes in natural plant products associated with their anti-Candida growth activity during two distinct seasonal changes—monsoon and summer. The potential of the salt marshes to inhibit the growth of five different Candida strains was assessed using four solvents. In phytochemical analysis, the extracts obtained from a Launaea sarmentosa exhibited the highest results compared to the other plant extracts. Fourier transform infrared spectroscopy revealed 12 peaks with alkane, aldehyde, amine, aromatic ester, phenol, secondary alcohol, and 1,2,3,4-tetrasubstituted. Gas-chromatography–mass spectrometry detected 30 compounds. Cyclotetracosane, lupeol, β-amyrin, and 12-oleanen-3-yl acetate showed the highest peak range. In particular, plant samples collected during the monsoon season were more effective in preventing Canda growth than the summer plant samples. In the monsoon season, the salt marsh plant extracted with ethyl acetate showed a high anti-Candida growth activity, while in the summer, the acetone extract exhibited a higher anti-Candida growth activity than the other solvents. The hexane extract of L. sarmentosa showed the highest inhibition zone against all Candidal strains. Furthermore, compounds, such as β-amyrin, lupeol, and oxirane, from the hexane extract of L. sarmentosa play a vital role in anti-Candida activity. This paper reports the potential of tidal marsh plant extracts for developing new antifungal agents for Candida infections. Full article

Currently, the spread of fungal infections is becoming an urgent problem. Fungi of the Candida genus are opportunistic microorganisms that cause superficial and life-threatening systemic candidiasis in immunocompromised patients. The list of antifungal drugs for the treatment of candidiasis is very limited, while the prevalence of resistant strains is growing rapidly. Therefore, the search for new antimycotics, including those exhibiting immunomodulatory properties, is of great importance. Plenty of natural compounds with antifungal activities may be extremely useful in solving this problem. This review evaluates the features of natural antimicrobial peptides, namely plant defensins as possible prototypes of new anticandidal agents. Plant defensins are important components of the innate immune system, which provides the first line of defense against pathogens. The introduction presents a brief summary regarding pathogenic Candida species, the pathogenesis of candidiasis, and the mechanisms of antimycotic resistance. Then, the structural features of plant defensins, their anticandidal activities, their mechanisms of action on yeast-like fungi, their ability to prevent adhesion and biofilm formation, and their combined action with conventional antimycotics are described. The possible mechanisms of fungal resistance to plant defensins, their cytotoxic activity, and their effectiveness in in vivo experiments are also discussed. In addition, for the first time for plant defensins, knowledge about their immunomodulatory effects is also presented. Full article

Candidiasis is considered an emerging public health concern because of the occurrence of drug-resistant Candida strains and the lack of an available structurally diverse antifungal drug armamentarium. The indole alkaloid globospiramine from the anticandidal Philippine medicinal plant Voacanga globosa exhibits a variety of biological activities; however, its antifungal properties remain to be explored. In this study, we report the in vitro anticandidal activities of globospiramine against two clinically relevant Candida species (C. albicans and C. tropicalis) and the exploration of its possible target proteins using in silico methods. Thus, the colony-forming unit (CFU) viability assay revealed time- and concentration-dependent anticandidal effects of the alkaloid along with a decrease in the number of viable CFUs by almost 50% at 60 min after treatment. The results of the MIC and MFC assays indicated inhibitory and fungicidal effects of globospiramine against C. albicans (MIC = 8 µg/mL; MFC = 8 µg/mL) and potential fungistatic effects against C. tropicalis at lower concentrations (MIC = 4 µg/mL; MFC > 64 µg/mL). The FAM-FLICA poly-caspase assay showed metacaspase activation in C. albicans cells at concentrations of 16 and 8 µg/mL, which agreed well with the MIC and MFC values. Molecular docking and molecular dynamics simulation experiments suggested globospiramine to bind strongly with 1,3-β-glucan synthase and Als3 adhesin—enzymes indirectly involved in apoptosis-driven candidal inhibition. Full article

Vulvovaginal candidiasis (VVC) is the most common cause of vaginal discharge among women. The present study aimed to investigate the synergistic anticandidal effect of lactobacillus cultures supplemented with plant extracts. Among 600 isolates of lactic acid bacteria, 41 isolates exhibited inhibitory activity against Candida albicans ATCC10231. Six out of 41 cell-free supernatants demonstrated the most potent antibacterial and anticandidal activities. They also inhibited the clinical isolates of C. albicans, causing VVC and non-C. albicans. The synergistic effect between Lactobacillus crispatus 84/7 and Limosilactobacillus reuteri 89/4 was demonstrated by the lowest fractional inhibitory concentration index (FICI = 0.5). The synbiotic culture of bacterial combination, cultured with Jerusalem artichoke (H. tuberosus) extract, also exhibited the strongest inhibition against the tested C. albicans. Biofilm formation decreased after 12 h of incubation in the selected cell-free supernatants of this synbiotic culture. The anticandidal activity of crude extracts was lost after treatment with proteinase K and trypsin but not with heating conditions, suggesting that it may be a heat-stable substance. In conclusion, the combination of L. crispatus 84/7 and L. reuteri 89/4 with H. tuberosus may be a promising candidate for inhibiting Candida infection and biofilm formation, with the potential use as ingredients in vaginal biotherapeutic products. Full article

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

Our aims in this work are the preparation of an ionic liquid based on heterocyclic compounds with Ag nanoparticles and the investigation of its application as an antibacterial and anticandidal agent. These goals were achieved through the fabrication of an ionic liquid based on Ag nanoparticles with 5-Amino-3-(4-fluorophenyl)-N-hexadecyl-7-(4-methylphenyl)-2-H spiro[cyclohexane1,2’-[1,3]thiazolo [4,5-b]pyridine]-6-carbonitrile (P16). The nanostructure of the prepared ionic liquid was characterized using techniques such as FTIR, ¹HNMR, ¹³CNMR, UV, SEM, and TEM. The biological activity of the prepared compound (P16) and its nanocomposites with Ag nanoparticles was tested using five clinical bacteria (Pseudomonas aeruginosa 249; Escherichia coli 141; Enterobacter cloacae 235; Staphylococcus epidermidis BC 161, and methicillin-resistant S. aureus 217), and three Candida species (Candida utilis ATCC 9255; C. tropicalis ATCC 1362, and C. albicans ATCC 20402). The FTIR, ¹HNMR, and ¹³CNMR results confirmed the chemical structure of the synthesized P16 compound. The nanostructure of the prepared ionic liquid was determined based on data obtained from the UV, SEM, and TEM tests. The antibacterial and anticandidal results showed that the biological activity of the compound (P16) was enhanced after the formation of nanocomposite structures with Ag nanoparticles. Moreover, the biological activity of the compound itself (P16) and that of its nanocomposite structure with Ag nanoparticles was higher than that of ampicillin and amphotericin B, which were used as control drugs in this work. Full article

Staphylococcus and Candida are recognized as causative agents in numerous diseases, and the rise of multidrug-resistant strains emphasizes the need to explore natural sources, such as fungi, for effective antimicrobial agents. This study aims to assess the in vitro anti-staphylococcal and anti-candidal potential of ethyl acetate extracts from various soil-derived fungal isolates. The investigation includes isolating and identifying fungal strains as well as determining their antioxidative activities, characterizing their phenolic substances through HPLC analysis, and conducting in silico molecular docking assessments of the phenolics’ binding affinities to the target proteins, Staphylococcus aureus tyrosyl-tRNA synthetase and Candida albicans secreted aspartic protease 2. Out of nine fungal species tested, two highly potent isolates were identified through ITS ribosomal gene sequencing: Aspergillus terreus AUMC 15447 and A. nidulans AUMC 15444. Results indicated that A. terreus AUMC 15447 and A. nidulans AUMC 15444 extracts effectively inhibited S. aureus (concentration range: 25–0.39 mg/mL), with the A. nidulans AUMC 15444 extract demonstrating significant suppression of Candida spp. (concentration range: 3.125–0.39 mg/mL). The A. terreus AUMC 15447 extract exhibited an IC₅₀ of 0.47 mg/mL toward DPPH radical-scavenging activity. HPLC analysis of the fungal extracts, employing 18 standards, revealed varying degrees of detected phenolics in terms of their presence and quantities. Docking investigations highlighted rutin as a potent inhibitor, showing high affinity (−16.43 kcal/mol and −12.35 kcal/mol) for S. aureus tyrosyl-tRNA synthetase and C. albicans secreted aspartic protease 2, respectively. The findings suggest that fungal metabolites, particularly phenolics, hold significant promise for the development of safe medications to combat pathogenic infections. Full article

Candida albicans and non-albicans Candida species are a common cause of human mucosal infections, as well as bloodstream infections and deep mycoses. The emergence of resistance of Candida spp. to antifungal drugs used in practice requires the search for new antimycotics. The present study unravels the antifungal potential of the synthetic dialk(en)ylthiosulfinates in comparison with an enzymatic in situ methionine γ-lyase-based thiosulfinate generation system (TGS). The kinetics of the TGS reaction, namely, the methionine γ-lyase-catalyzed β-elimination of S-alk(en)yl-L-cysteine sulfoxides, was investigated via ¹H NMR spectroscopy for the first time, revealing fast conversion rates and the efficient production of anticandidal dialk(en)ylthiosulfinates. The anticandidal potential of this system vs. synthetic thiosulfinates was investigated through an in vitro assay. TGS proved to be more effective (MIC range 0.36–1.1 μg/mL) than individual substances (MIC range 0.69–3.31 μg/mL). The tested preparations had an additive effect with the commercial antimycotics fluconazole, amphotericin B and 5-flucytosine demonstrating a fractional inhibitory coefficient index in the range of 0.5–2 μg/mL. TGS can be regarded as an attractive candidate for the targeted delivery of antimycotic thiosulfinates and for further implementation onto medically implanted devices. Full article