Characterization and biological activity of selenium nanoparticles biosynthesized by Yarrowia lipolytica.

In this research, biogenic selenium nanoparticles were produced by the fungi Yarrowia lipolytica, and the biological activity of its nanoparticles was studied for the first time. The electron microscopy analyses showed the production of nanoparticles were intracellular and the resulting particles were extracted and characterized by XRD, zeta potential, FESEM, EDX, FTIR spectroscopy and DLS. These analyses showed amorphous spherical nanoparticles with an average size of 110 nm and a Zeta potential of -34.51 ± 2.41 mV. Signatures of lipids and proteins were present in the capping layer of biogenic selenium nanoparticles based on FTIR spectra. The antimicrobial properties of test strains showed that Serratia marcescens, Klebsiella pneumonia, Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis were inhibited at concentrations between 160 and 640 µg/mL, while the growth of Candida albicans was hindered by 80 µg/mL of biogenic selenium nanoparticles. At concentrations between 0.5 and 1.5 mg/mL of biogenic selenium nanoparticles inhibited up to 50% of biofilm formation of Klebsiella pneumonia, Acinetobacter baumannii, Staphylococcus aureus and Pseudomonas aeruginosa. Additionally, the concentration of 20-640 µg/mL of these bioSeNPs showed antioxidant activity. Evaluating the cytotoxicity of these nanoparticles on the HUVEC and HepG2 cell lines did not show any significant toxicity within MIC concentrations of SeNPs. This defines that Y. lipolytica synthesized SeNPs have strong potential to be exploited as antimicrobial agents against pathogens of WHO concern.

Eco-friendly synthesis of bioactive silver nanoparticles from black roasted gram (Cicer arietinum) for biomedical applications.

Green synthesis leverages biological resources such as plant extracts to produce cost-effectively and environmentally friendly NPs. In our study, silver nanoparticles (AgNPs) are biosynthesized using blank roasted grams (Cicer arietinum) as reducing agents. CA-AgNPs were characterized by a characteristic surface plasmon resonance (SPR) peak at 224 nm in the UV-Vis spectrum. FTIR analysis revealed functional groups with O-H stretching at 3410 cm-1, C-H stretching at 2922 cm-1, and C=O stretching at 1635 cm-1. XRD patterns exhibited sharp peaks at 33.2°, 38.4°, 55.7°, and 66.6°, confirming high crystallinity. Morphological analysis through FESEM indicated spherical CA-AgNPs averaging 500 nm in size, with EDS revealing Ag at 97.51% by weight. Antimicrobial assays showed zones of inhibition of 14 mm against Candida albicans, 18 mm against Escherichia coli., and 12 mm against Propionibacterium acnes. The total phenolic content of CA-AgNPs was 26.17 ± 13.54 mg GAE/g, significantly higher than the 11.85 ± 9.57 mg GAE/g in CA extract. The ABTS assay confirmed the antioxidant potential with a lower IC50 value of 1.73 ± 0.41 µg/mL, indicating enhanced radical scavenging activity. Anti-melanogenesis was validated through tyrosinase, showing inhibition rates of 97.97% at the highest concentrations. The anti-inflammatory was evaluated by western blot, which showed decreased expression of iNOS and COX-2. This study demonstrates the green synthesis of CA-AgNPs and its potential biomedical applications. The results of this study demonstrate that biosynthesized CA-AgNPs have key biological applications.

Standardisation of high throughput microdilution antifungal susceptibility testing for Candida albicans and Cryptococcus neoformans.

The Clinical and Laboratory Standards Institute (CLSI) M27 guidelines are the recommended and most commonly used protocols for broth microdilution antifungal susceptibility testing of yeasts. However, these guidelines are limited to the use of 96-well assay plates, limiting assay capacity. With the increased risk of fungal resistance emerging in the community, it is important to have alternative protocols available, that offer higher throughput and can screen more than eight to ten potential antifungal compounds per plate. This study presents an optimised broth microdilution minimum inhibitory concentration (MIC) method for testing the susceptibility of yeasts in an efficient high throughput screening setup, with minimal growth variability and maximum reproducibility. We extend the M27 guidelines and optimise the conditions for 384-well plates. Validation of the assay was performed with ten clinically used antifungals (fluconazole, amphotericin B, 5-fluorocytosine, posaconazole, voriconazole, ketoconazole, itraconazole, caspofungin diacetate, anidulafungin and micafungin) against Candida albicans and Cryptococcus neoformans.

Hyphal swelling induced in the phagosome of macrophages.

Macrophages play critical protective roles as sentinels of the innate immune system against fungal infection. It is therefore important to understand the dynamics of the interaction between these phagocytes and their fungal prey. We show here that many of the hyphal apices formed by Candida albicans within the macrophage ceased elongating, and apical and sub-apical hyphal compartments became swollen. Swollen hyphal cell compartments assimilated less Lysotracker-Red than non-swollen compartments, suggesting they had enhanced viability. Staining with florescent dyes suggested that there were higher levels of ß-glucan and chitin in internalized fungal filaments compared to non-internalized hyphae, suggesting active cell wall remodelling within macrophages. These observations suggest that the stresses imposed by macrophages upon the fungus lead to changes in cell wall composition, inhibition of polarised growth and the induction of swelling in hyphal compartments, and that this can prevent or delay loss of viability of hyphal cells within the phagocyte.

Tissue response in a rat model of denture stomatitis treated with tissue conditioner containing antifungal complexed with ß-cyclodextrin.

Introduction. Tissue conditioners modified with antifungals are a potential alternative to denture stomatitis (DS) treatment.Gap Statement. Information on tissue response to this treatment before its clinical application is lacking.Aim. This study aimed to evaluate the tissue response of a tissue conditioner modified with antifungals in a rat model of DS.Methodology. After DS induction for 4 days under antibiotic therapy, Wistar rats had their intraoral devices (IODs) relined with the tissue conditioner Softone without (Soft) or with the MICs against Candida albicans of nystatin (Nys) or chlorhexidine (Chx) complexed or not with ß-cyclodextrin (Nys:ßCD and Chx:ßCD). Three controls were included: healthy rats [negative control (Nc)], rats using a sterile IOD [sterile device (Sd)] and rats with DS that did not receive treatment (DS). After 4 days of treatment, the palatal mucosa under the IODs underwent histological processing for morphohistopathological and histometric analyses, morphology of collagen fibres (birefringence), immunohistochemistry for the expression of cell proliferation (proliferating cell nuclear antigen) and cytokine (IL-1ß).Results. The Nc and Sd groups were similar (P>0.05), displaying epithelial and connective tissues without any discernible changes in the parameters assessed. The DS and Soft groups exhibited pronounced epithelial alterations, cell proliferation and expression of the cytokine IL-1ß. In groups treated with drug incorporation (Nys, Chx, Nys:ßCD and Chx:ßCD), all samples demonstrated a reduction in tissue inflammation or complete tissue recovery, with an epithelium compatible with health. For the immunohistochemical parameters, the Chx, Nys:ßCD and Chx:ßCD groups were comparable with Nc (P>0.05).Conclusion. The proposed treatment could be promising for DS, as it led to the tissue recovery of the palatal mucosa. Nevertheless, much lower concentrations of complexed antifungals were required to achieve a similar or higher degree of tissue response compared with uncomplexed drugs in a modified tissue conditioner formulation.

[Invasive candidiasis]. / Candidose invasive.

Candida spp is responsible for 70-90% of invasive fungal infections. Invasive candidiasis is usually diagnosed by blood culture; other microbiological methods such as PCR, beta-D-glucans and mannans/anti-mannans are available in addition to clinical scores such as the Candida score. Management includes antifungal therapy, removal of catheters and source control, follow-up blood cultures and fundus examination, one possible complication being endophthalmitis. Candida albicans is the most common species in Switzerland and is generally susceptible to all antifungal agents. One concern is the spread of Candida auris, due to multi-resistant strains and the propensity to spread within and between hospitals, which is difficult to control.

Candida spp. est responsable de 70-90 % des infections fongiques invasives. La candidose invasive est généralement diagnostiquée par hémoculture ; d'autres méthodes microbiologiques telles que la PCR, les bêta-D-glucans et les mannanes/anti-mannanes sont disponibles, auxquelles s'ajoutent des scores cliniques tels que le Candida score. La prise en charge comprend un antifongique, le retrait des cathéters et un contrôle de la source, des hémo­cultures de suivi et la réalisation d'un examen du fond d'œil, l'une des complications possibles étant l'endophtalmite. Le Candida albicans est l'espèce la plus répandue en Suisse et généralement sensible à tous les antifongiques. Une crainte est la diffusion de Candida auris en raison de souches multirésistantes et d'une propension à la dissémination intra et interhospitalière difficile à contrôler.

Concentration-Dependent Effects of MXene Nanocomposite-Loaded Carboxymethyl Cellulose on Wound Healing.

Nanoparticles (NPs) have emerged as a promising solution for many biomedical applications. Although not all particles have antimicrobial or regenerative properties, certain NPs show promise in enhancing wound healing by promoting tissue regeneration, reducing inflammation, and preventing infection. Integrating various NPs can further enhance these effects. Herein, the zinc oxide (ZnO)-MXene-Ag nanocomposite was prepared, and the conjugation of its three components was confirmed through scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) mapping analysis. In vitro analysis using the agar well diffusion technique demonstrated that ZnO-MXene-Ag nanocomposite exhibited high antimicrobial efficacy, significantly inhibiting Escherichia coli, Salmonella, and Candida albicans, and showing enhanced potency when combined with tetracycline, resulting in a 2.6-fold increase against Staphylococcus and a 2.4-fold increase against Pseudomonas. The efficacy of nanocomposite-loaded carboxymethyl cellulose (CMC) gel on wound healing was investigated using varying concentrations (0, 1, 5, and 10 mg/mL). Wound healing was monitored over 21 days, with results indicating that wounds treated with 1 mg/mL ZnO-MXene-Ag gel exhibited superior healing compared to the control group (0 mg/mL), with significant improvements noted from Day 3 onward. Conversely, higher concentrations (10 mg/mL) resulted in reduced healing efficiency, particularly notable on Day 15. In conclusion, the ZnO-MXene-Ag nanocomposite-loaded CMC gel is a promising agent for enhanced wound healing and antimicrobial applications. These findings highlight the importance of optimizing NP concentration to maximize therapeutic benefits while minimizing potential cytotoxicity.

Development of synergistic antifungal in situ gel of miconazole nitrate loaded microemulsion as a novel approach to treat vaginal candidiasis.

Limited solubility is the main cause of the low local availability of anti-candidiasis drug, miconazole nitrate (MN). The study's objective was to develop and characterize microemulsion (ME) based temperature-triggered in situ gel of MN for intravaginal administration to enhance local availability and antifungal activity. The solubility of MN was initially studied in different oils, surfactants, and co-surfactants. Then, pseudo-ternary phase diagrams were constructed to select the best ratio of various components. The ME formulations were characterized by thermodynamic study, droplet size, polydispersity index (PDI), viscosity, and in-vitro antifungal mean inhibition zone (MIZ). Selected MEs were incorporated into different in situ gel bases using a combination of two thermosensitive polymers (poloxamer (PLX) 407 and 188), with 0.6% of hydroxypropyl methylcellulose (HPMC K4M) and gellan gum (GG) as mucoadhesive polymer. ME-based gels (MG) were investigated for gelation temperature, gelation time, viscosity, spreadability, mucoadhesive strength, in vitro release profile, and MIZ test. Furthermore, the optimum MG was assessed for in vivo animal irritation test and FESEM investigation. Tea tree oil, lavender oil, tween 80, and propylene glycol (PG) were chosen for ME preparation for the optimal formulation; formulation ME7 and ME10 were chosen. After incorporation of the selected formulation into a mixture of P407 and P188 (18:2% w/w) with 0.6% mucoadhesive polymer, the resultant MG formulation (MG1) revealed optimum gelation temperature (33 ± 0.01℃) and appropriate viscosity with enhanced sustained release (98%) and retention through sheep vaginal mucosa, MG1 exhibited a better MIZ compared to the 2% MN gel formulation and the marketed MN product, and no rabbit vagina irritation. In conclusion, the miconazole nitrate-loaded MG-based formula sustained the duration of action and better antifungal activity than the marketed miconazole nitrate formulation.

Histone-like transcription factor Hfl1p in Candida albicans harmonizes nuclear and mitochondrial genomic network in regulation of energy metabolism and filamentation development.

Candida albicans is an opportunistic fungal pathogen known for surviving in various nutrient-limited conditions within the host and causing infections. Our prior research revealed that Hfl1p, an archaeal histone-like or Hap5-like protein, is linked to mitochondrial ATP generation and yeast-hyphae morphogenesis. However, the specific roles of Hfl1p in these virulence behaviours, through its function in the CBF/NF-Y complex or as a DNA polymerase II subunit, remain unclear. This study explores Hfl1p's diverse functions in energy metabolism and morphogenesis. By combining proteomic analysis and phenotypic evaluations of the hfl1Δ/hfl1Δ mutant with ChIP data, we found that Hfl1p significantly impacts mitochondrial DNA-encoded CI subunits, the tricarboxylic acid (TCA) cycle, and morphogenetic pathways. This influence occurs either independently or alongside other transcription factors recognizing a conserved DNA motif (TAXXTAATTA). These findings emphasize Hfl1p's critical role in linking carbon metabolism and mitochondrial respiration to the yeast-to-filamentous form transition, enhancing our understanding of C. albicans' metabolic adaptability during morphological transition, an important pathogenic trait of this fungus. This could help identify therapeutic targets by disrupting the relationship between energy metabolism and cell morphology in C. albicans.

Effects of photodynamic therapy using bisdemethoxycurcumin combined with melatonin or acetyl-melatonin on C. Albicans.

The current study aims to explore the efficacy of antifungal photodynamic therapy (PDT) on C. albicans biofilms by combining photosensitizers, bisdemethoxycurcumin (BDMC), and melatonin (MLT) or acetyl-melatonin (AcO-MLT). Additionally, the relationship between different types of reactive oxygen species and PDT's antifungal efficacy was investigated. BDMC, MLT and AcO-MLT were applied, alone and in combination, to 48-hour C. albicans biofilm cultures (n = 6/group). Blue and red LED light (250 mW/cm2 with 37.5 J/cm2 for single or 75 J/cm2 for dual photosensitizer groups) were used to irradiate BDMC groups and MLT/AcO-MLT groups, respectively. For combination groups, blue LEDs and subsequently red LEDs were used. Drop plate assays were performed at 0, 1 and 6 h post-treatment. Colony forming units (CFUs) were then counted after 48 h. Hydroxyl radicals and singlet oxygen were measured using fluorescence spectroscopy and electron spin resonance (ESR) spectroscopy. Additionally, cell cytotoxicity was tested on human oral keratinocytes. Significant CFU reductions were observed with combinations 20 µM BDMC + 20 µM AcO-MLT and 60 µM BDMC + 20 µM MLT at 0 and 1 h post-treatment, respectively. Singlet oxygen production increased with the addition of MLT/AcO-MLT and had moderate-substantial correlations with inhibition at all times. Hydroxyl radical production was not significantly different from the control. Additionally, BDMC exhibited subtle cytotoxicity on human oral keratinocytes. PDT using BDMC + MLT or AcO-MLT, with blue and red LED light, effectively inhibits C. albicans biofilm through singlet oxygen generation. Melatonin acts as a photosensitizer in PDT to inhibit fungal infection.

Enhancing antifungal and antibacterial properties of denture resins with nystatin-coated silver nanoparticles.

Long-term oral health issues caused by fungi and bacteria are a primary concern for individuals who wear dentures. Denture stomatitis, primarily caused by Candida albicans (C. albicans), is a prevalent condition among denture users. Metal nanoparticles exhibit improved antimicrobial effectiveness and fewer adverse effects. This study aimed to evaluate the antifungal and antibacterial effects of nystatin-coated silver nanoparticles (Nys-coated AgNPs) embedded in acrylic resin as a more biocompatible material for denture resins. AgNPs and Nys-coated AgNPs were synthesized and characterized using UV-Vis, SEM, EDX, and DLS. Specimens of polymethyl methacrylate (PMMA) with three different concentrations of Nys, AgNPs, and Nys-coated AgNPs (0.1%, 1%, 10% w/w) were prepared. The water absorption properties of the disks and drug release were investigated for 14 days and 120 h, respectively. The hydrophilic and hydrophobic properties of the samples and their contact angles were evaluated using the sessile drop technique. The antifungal and antimicrobial activity of the prepared discs was studied against C. albicans and Streptococcus mutans, respectively. Adding Nys-coated AgNPs decreased the contact angle of discs from 67° to 49°. Furthermore, the water absorption rates of the different discs were not significantly different from those of the control groups. Results showed that Nys-coated AgNPs (10% w/w) in PMMA effectively inhibited C. albicans growth better than Nys composites (10% w/w). Additionally, Nys-coated AgNPs composites, as well as AgNPs-containing composites, showed considerable antibacterial activity against S. mutans. Nys-coated AgNPs (10% w/w) had no toxic effect on NIH3T3 cells. In conclusion, Nys-coated AgNPs could be considered a good candidate for incorporation into denture resins to address chronic oral diseases.

A dataset for developing proteomic tools for pathogen detection via differential cell lysis of whole blood samples.

This data descriptor presents a curated dataset for pathogen detection and identification (Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans) directly from whole-blood samples. The dataset was created using differential cell lysis combined with rapid extraction, digestion, and mass spectrometry-based proteomics. Our method offers a rapid diagnostic alternative to traditional culture, enabling timely disease management, such as sepsis. Highlighting our dataset's uniqueness, it features a three-tier structure: Spectral Libraries of Pathogens for identifying peptide peaks for putative biomarkers; Spiked pathogen in blood MS data for biomarker panel optimization through varied concentration samples; and Parallel Reaction Monitoring (PRM) data from sepsis patients for validating our biomarker panel, achieving 83.3% sensitivity within seven hours without microbial enrichment culture. This dataset serves as a comprehensive reference for bioinformatic tool development and biomarker panel proposals, advancing microbial detection, antimicrobial resistance, and epidemiological studies.

Cases of endophthalmitis caused by Candida albicans and Candida dubliniensis identified via internal transcribed spacer deep sequencing.

BACKGROUND: We report two cases of fungal endophthalmitis induced by Candida species identified based on internal transcribed spacer 1 (ITS1) sequencing. CASE PRESENTATION: In two cases, endophthalmitis was suspected, and the patients underwent pars plana vitrectomy. Case 1 was a 64-year-old woman with a history of cataract surgery 10 days prior. She had a history of anal primary melanoma, which metastasized throughout the body and subsequently relapsed. Vitreous culture and ITS-1 deep sequencing revealed the presence of the rare fungus, Candida dubliniensis. Case 2 was a 54-year-old man with a history of liver cancer and kidney failure. Culture methods and ITS1 deep sequencing both revealed the presence of Candida albicans. Both patients exhibited good visual prognoses after treatment with topical and systemic antibiotics. CONCLUSIONS: We present two cases of fungal endophthalmitis caused by two Candida species identified by both the culture method and ITS1 deep sequencing. The fungal pathogen was identified by ITS deep sequencing three days after sample submission; the culture method yielded results after 1 week. These findings support the applicability of ITS1 sequencing for timely pathogen identification for cases of fungal endophthalmitis and provide detailed taxonomic information at the species level.

Specific cell subclusters of dental pulp stem cells respond to distinct pathogens through the ROS pathway.

Introduction: Microbial pathogens invade various human organs, including the oral cavity. Candida albicans (C.a) and Streptococcus mutans (S.m) served respectively as representative oral pathogenic fungi and bacteria to stimulate dental pulp stem cells (DPSCs) and to screen the DPSC subcluster that specifically responded to fungal infection. Methods: DPSCs were obtained from the impacted third molars of six healthy subjects. Then, cells were mixed and divided into three samples, two of which were stimulated with C.a and S.m, respectively; the third sample was exposed to cell medium only (Ctrl). Single-cell mRNA sequencing analysis of treated DPSCs was performed. Results: DPSCs were composed of four major clusters of which one, DPSC.7, exhibited unique changes compared to those of other subclusters. The DPSC.7 cell percentage of the C.a sample was twice those of the Ctrl and S.m samples. DPSC.7 cells expressed genes associated with the response to reactive oxygen species (ROS) response. DPSC.7 subgroup cells established characteristic aggregation under the stimulation of different pathogens in UMAP. The MAPK/ERK1/2 and NF-κB pathways were up-regulated, DUSP1/5/6 expressions were suppressed, FOS synthesis was activated, the immune-related pathway was induced, and the levels of cytokines, including IL-6 and CCL2, were up-regulated in DPSC.7 cells when stimulated with C.a. Conclusions: Our study analyzed the cellular and molecular properties of DPSCs infected by oral fungi and bacteria with single-cell RNA sequencing. A subcluster of DPSCs responded specifically to infections with different pathogens, activating the MAPK and NF-κB pathways to induce immune responses via the ROS pathway. This suggests novel treatment strategies for fungal infections.

The Cytochalasins and Polyketides from a Mangrove Endophytic Fungus Xylaria arbuscula QYF.

Twelve compounds, including four undescribed cytochalasins, xylariachalasins A-D (1-4), four undescribed polyketides (5-8), and four known cytochalasins (9-12), were isolated from the mangrove endophytic fungus Xylaria arbuscula QYF. Their structures and absolute configurations were established by extensive spectroscopic analyses (1D and 2D NMR, HRESIMS), electronic circular dichroism (ECD) calculations, 13C NMR calculation and DP4+ analysis, single-crystal X-ray diffraction, and the modified Mosher ester method. Compounds 1 and 2 are rare cytochalasin hydroperoxides. In bioactivity assays, Compound 2 exhibited moderate antimicrobial activities against Staphylococcus aureus and Candida albicans with MIC values of 12.5 µM for both Compound 10 exhibited significant cytotoxic activity against MDA-MB-435 with an IC50 value of 3.61 ± 1.60 µM.

An in vitro set-up to study Pdr5-mediated substrate translocation.

Pdr5 is the most abundant ABC transporter in Saccharomyces cerevisiae and plays a major role in the pleiotropic drug resistance (PDR) network, which actively prevents cell entry of a large number of structurally unrelated compounds. Due to a high level of asymmetry in one of its nucleotide binding sites (NBS), Pdr5 serves as a perfect model system for asymmetric ABC transporter such as its medical relevant homologue Cdr1 from Candida albicans. In the past 30 years, this ABC transporter was intensively studied in vivo and in plasma membrane vesicles. Nevertheless, these studies were limited since it was not possible to isolate and reconstitute Pdr5 in a synthetic membrane system while maintaining its activity. Here, the functional reconstitution of Pdr5 in a native-like environment in an almost unidirectional inside-out orientation is described. We demonstrate that reconstituted Pdr5 is capable of translocating short-chain fluorescent NBD lipids from the outer to the inner leaflet of the proteoliposomes. Moreover, this transporter revealed its ability to utilize other nucleotides to accomplish transport of substrates in a reconstituted system. Besides, we were also able to estimate the NTPase activity of reconstituted Pdr5 and determine the kinetic parameters for ATP, GTP, CTP, and UTP.

Identification of lovastatin production in Aspergillus terreus strain (KF971363.1) and its antifungal role.

Lovastatin has received interest for its potential therapeutic use in treating numerous diseases, for example, the blood cholesterol level by restraining hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The research utilized the fungal growth bioassay technique to disengage and evaluate filamentous organism for the lovastatin creation. The clever type of Aspergillus terreus (KF971363.1) was embraced for lovastatin creation by solid-state fermentation (SSF). Lovastatin production was optimized using physiological parameters such as pH and temperature at SSF. The addition of nitrogen source enhanced the production of lovastatin by the breakdown of lignocellulose that improved the production of lovastatin. The research verified a yeast growth inhibition bioassay approach, in addition to thin-layer chromatography and liquid chromatography-mass spectrometry (LC-MS). All of these techniques were used to confirm lovastatin production. The purified extract subjected to the TLC analysis showed retention factor (Rf) value of 0.73. Moreover, the inhibition bioassay method reassures the lovastatin production by comparing the zone of inhibition against C. albicans.

Antifungal Activity and Multi-Target Mechanism of Action of Methylaervine on Candida albicans.

The discovery of a lead compound against Candida albicans is urgently needed because of the lack of clinically available antifungal drugs and the increase in drug resistance. Herein, a ß-carboline alkaloid methylaervine (MET) exhibited potential activity against C. albicans (MIC = 16-128 µg/mL), no hemolytic toxicity, and a low tendency to induce drug resistance. An antifungal mechanism study indicated that MET effectively inhibited the biofilm formation and disrupted the mature biofilm. Moreover, filamentation formation and spore germination were also weakened. The electron microscopy analysis revealed that MET could damage the cell structure, including the cell wall, membrane, and cytoplasm. In particular, the permeability and integrity of the cell membrane were destroyed. When it entered the fungi cell, it interfered with the redox homeostasis and DNA function. Overall, MET can inhibit the growth of C. albicans from multiple channels, such as biofilm, filamentation, cell structure, and intracellular targets, which are difficult to mutate at the same time to generate drug resistance. This work provides a promising lead compound for the creation of new antifungal agents against C. albicans.

Mechanisms of action of Lactobacillus spp. in the treatment of oral candidiasis.

Candida albicans is often associated with oral candidiasis, and drug-resistance profiles have contributed to an increase in morbidity and mortality. It is known that Lactobacillus spp. acts by competing for adhesion to the epithelium, absorption of nutrients and modulation of the human microbiota. Therefore, they are important to assist in the host's microbiological balance and reduce the growth of Candida spp. Until now, there have been no reports in the literature of reviews correlating to the use of Lactobacillus spp. in the treatment of oral candidiasis. Thus, this review aims to highlight the mechanisms of action of Lactobacillus spp. and methods that can be used in the treatment of oral candidiasis. This is a study carried out through the databases PubMed Central and Scientific Electronic Library Online, using the following keywords: Oral Candidiasis and Lactobacillus. Original articles about oral candidiasis were included, with both in vitro and in vivo analyses, and published from 2012 to 2022. Lactobacillus rhamnosus was the most common microorganism used in the experiments against Candida, acting mainly in the reduction of biofilm, filamentation, and competing for adhesion sites of Candida spp. Among in vivo studies, most researchers used immunosuppressed mouse modelsof Candida infection. The studies showed that Lactobacillus has a great potential as a probiotic, acting mainly in the prevention and treatment of mucosal diseases. Thus, the use of Lactobacillus may be a good strategy for the treatment of oral candidiasis.