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ABSTRACT Biofilms are recalcitrant to antimicrobials, partly due to the barrier effect of their matrix. The use of hydrolytic enzymes capable to degrade matrix constituents has been proposed as an alternative strategy against biofilm-related infections. This study aimed to determine whether hydrolytic enzymes could potentiate the activity of antimicrobials against hard-to-treat interkingdom biofilms comprising two bacteria and one fungus. We studied the activity of a series of enzymes alone or in combination, followed or not by antimicrobial treatment, against single-, dual- or three-species biofilms of Staphylococcus aureus, Escherichia coli, and Candida albicans, by measuring their residual biomass or culturable cells. Two hydrolytic enzymes, subtilisin A and lyticase, were identified as the most effective to reduce the biomass of C. albicans biofilm. When targeting interkingdom biofilms, subtilisin A alone was the most effective enzyme to reduce biomass of all biofilms, followed by lyticase combined with an enzymatic cocktail composed of cellulase, denarase, and dispersin B that proved previously active against bacterial biofilms. The subsequent incubation with antimicrobials further reduced the biomass. Enzymes alone did not reduce culturable cells in most cases and did not interfere with the cidal effects of antimicrobials. Therefore, this work highlights the potential interest of pre-exposing interkingdom biofilms to hydrolytic enzymes to reduce their biomass besides the number of culturable cells, which was not achieved when using antimicrobials alone. IMPORTANCE Biofilms are recalcitrant to antimicrobial treatments. This problem is even more critical when dealing with polymicrobial, interkingdom biofilms, including both bacteria and fungi, as these microorganisms cooperate to strengthen the biofilm and produce a complex matrix. Here, we demonstrate that the protease subtilisin A used alone, or a cocktail containing lyticase, cellulase, denarase, and dispersin B markedly reduce the biomass of interkingdom biofilms and cooperate with antimicrobials to act upon these recalcitrant forms of infection. This work may open perspectives for the development of novel adjuvant therapies against biofilm-related infections.

The incidence of fungal infections has significantly increased in recent years due to the emergence of antifungal resistance. Biofilm formation is considered to be a major contributor to both the infectious diseases and to antimicrobial resistance. Consequently, biofilm-associated infections are often problematic to treat with existing therapeutics. Adhesion of C. albicans to the host surface or implanted materials followed by hyphal invasion and biofilm formation enhances C. albicans pathogenicity and virulence. Thus, developing a therapeutic agent that inhibits candidal adherence, biofilm development and morphological switching could improve clinical management of infections. The present investigation studied two emerging and alternatives strategies, namely antibiofilm and combinatorial approach, to attenuate biofilm formation and the expression of Candida virulence factors. Piperine and thymol are major bioactive components of pepper and thyme, respectively. These phytochemicals are known to possess numerous biological activities, including recently reported antibiofilm effects against C. albicans. The minimum biofilm inhibitory concentration (MBIC) of both phytochemicals was determined to be 32 µg/ml. The phytochemical treatment of Candida biofilms using piperine and thymol revealed synergistic effects at four different combinations of concentrations, i.e. 8 and 8, 8 and 4, 8 and 2 and 4 and 8 µg/ml. These synergistic combinations resulted in the significant reduction in adherence of Candida, hyphal extension and morphological transformation. Moreover, limited exposure of synergistic combinations controlled the hyphal elongation. Results were validated through the gene expression analysis. Results from the present investigation suggest that piperine and thymol can be synergistically employed for the treatment of biofilm-associated C. albicans infection.

As an alternative to fossil volatile hydrocarbon solvents used nowadays in perfumery, investigation on essential oil of Commiphora wildii Merxm. oleo gum resin as a source of heptane is reported here. Heptane, representing up to 30 wt-% of this oleo gum resin, was successfully isolated from the C. wildii essential oil, using an innovative double distillation process. Isolated heptane was then used as a solvent in order to extract some noble plants of perfumery. It was found that extracts obtained with this solvent were more promising in terms of sensory analysis than those obtained from fossil-based heptane. In addition, in order to valorize the essential oil depleted from heptane, chemical composition of this oil was found to obtain, and potential biological activity properties were studied. A total of 172 different compounds were identified by GC-MS in the remaining oil. In vitro tests—including hyaluronidase, tyrosinase, antioxidant, elastase and lipoxygenase, as well as inhibitory tests against two yeasts and 21 bacterial strains commonly found on the skin—were carried out. Overall, bioassays results suggest this heptane-depleted essential oil is a promising active ingredient for cosmetic applications.

Background and Aim: patients infected with HIV are susceptible to opportunistic infections such as candidiasis. In normal individuals, Candida spp. exist as normal flora of the mucous membranes. In this study we compared the frequencies of different species of Candida between HIV infected patients receiving anti-retroviral therapy (ART) and normal individuals. Materials and Methods: This case- control study included 60 HIV positive patients receiving antiviral therapy as our case group and 60 normal individuals as control group. Oral samples were prepared by two wet swabs and cultured on Sabouraud dextrose agar. Colonies grown on the culture medium were identified by phenotyping and molecular (PCR) methods at two different temperatures. Results: Candida species were isolated from the oral mucosa of 68.3% of HIV positive patients and 53.3% of normal individuals. Rate of colonization of oral cavity by candida showed no significant relationships with the variable parameters of TCD4+ (P = 0.12), viral load (P = 0.24), and duration of HIV infection (P = 0.92), but it had significant relationships with brushing (P= 0.001), smoking (P = 0.043) and drug abuse (P = 0.002). Conclusion: The result showed an increased shift of the yeast colonization from C.albicans to non- albicans species in HIV-infected subjects. Considering the susceptibility of this group to opportunistic infections such as candidiasis, regular and periodic monitoring of these patients is necessary. Tooth brushing, discontinuation of cigarette smoking and drug abuse, together with oral hygiene are recommended.

Background and Aim:patients infected with HIV are susceptible to opportunistic infections such as candidiasis. In normal individuals, Candidaspp. exist as normal flora of the mucous membranes. In this study we compared the frequencies of different species of Candidabetween HIV infected patients receiving anti-retroviral therapy (ART) and normal individuals .Materials and Methods:This case-control study included 60 HIV positive patients receiving antiviral therapy as our case group and 60 normal individuals as control group. Oral samples were prepared by two wet swabs and cultured on Sabouraud dextrose agar. Colonies grown on the culture medium were identified by phenotyping and molecular (PCR) methods at two different temperatures. Results:Candidaspecies were isolated from the oral mucosa of 68.3% of HIV positive patients and 53.3% of normal individuals. Rate of colonization of oral cavity by candida showed no significant relationships with the variable parameters of TCD4+ (P = 0.12), viral load (P = 0.24), and duration of HIV infection (P = 0.92), but it had significant relationships with brushing (P = 0.001), smoking (P = 0.043) and drug abuse (P = 0.002).Conclusion:The result showed an increased shift of the yeast colonization from C.albicansto non-albicans species in HIV-infected subjects. Considering the susceptibility of this group to opportunistic infections such as candidiasis, regular and periodic monitoring of these patients is necessary. Tooth brushing, discontinuation of cigarette smoking and drug abuse, together with oral hygieneare recommended.

Farnesol, a self-secreted quorum-sensing molecule (QSM) of Candida albicans, has been known to limit yeast-to-hyphal transition by blocking the RAS1–cAMP–PKA pathway. In a similar fashion, certain bacterial QSMs have also been reported to be successful in attenuating C. albicans biofilm and hyphal formation at relatively high cell density. This prompted us to investigate the antihyphal efficacy of certain bacterial QSMs through virtual docking against seminal drug targets, viz., CYCc and RAS1, that have been reported to be the hallmark players in C. albicans dimorphic virulence cascade. Against this backdrop, 64 QSMs belonging to five different bacterial QS signaling systems were subjected to initial virtual screening with farnesol as reference. Data of the virtual screening unveiled QSMs belonging to diketopiperazines (DKPs), i.e., 3-benzyl-6-isobutylidene-2,5-piperazinedione (QSSM 1157) and cyclo(l-Pro-l-Leu) (QSSM 1112), as potential inhibitors of CYCc and RAS1 with binding energies of −8.2 and −7.3 kcal mol−1, respectively. Further, the molecular dynamics simulations (for 50 ns) of CYCc-QSSM 1157 and RAS1-QSSM 1112 complexes revealed the mean ligand root mean square deviation (RMSD) values of 0.35 and 0.27 Å, respectively, which endorsed the rigid nature, less fluctuation in binding stiffness, and conformation of binding complexes. Furthermore, the identified two QSMs were found to be good in solubility, absorption, and permeation and less toxic in nature, as revealed by pharmacokinetics and toxicity analyses. In addition, the in vitro antihyphal assays using liquid and solid media, germ-tube experiment, and microscopic analysis strongly validated DKP-QSSM 1112 as a promising inhibitor of hyphal transition. Taken together, the present study unequivocally proves that DKPs can be used as potent inhibitors of C. albicans virulence dimorphism.

Mycoses infect millions of people annually across the world. The most common mycosis agent, Candida albicans is responsible for a great deal of illness and death. C. albicans infection is becoming more widespread and the current antifungals polyenes, triazoles, and echinocandins are less efficient against it. Investigating antifungal peptides (AFPs) as therapeutic is gaining momentum. Therefore, we used MALDI-TOF/MS analysis to identify AFPs and protein-protein docking to analyze their interactions with the C. albicans target protein. Some microorganisms with strong antifungal action against C. albicans were selected for the isolation of AFPs. Using MALDI-TOF/MS, we identified 3 AFPs Chitin binding protein (ACW83017.1; Bacillus licheniformis), the bifunctional protein GlmU (BBQ13478.1; Stenotrophomonas maltophilia), and zinc metalloproteinase aureolysin (BBA25172.1; Staphylococcus aureus). These AFPs showed robust interactions with C. albicans target protein Sap5. We deciphered some important residues in identified APFs and highlighted interaction with Sap5 through hydrogen bonds, protein-protein interactions, and salt bridges using protein-protein docking and MD simulations. The three discovered AFPs-Sap5 complexes exhibit different levels of stability, as seen by the RMSD analysis and interaction patterns. Among protein-protein interactions, the remarkable stability of the BBQ25172.1-2QZX complex highlights the role of salt bridges and hydrogen bonds. Identified AFPs could be further studied for developing successful antifungal candidates and peptide-based new antifungal therapeutic strategies as fresh insights into addressing antifungal resistance also., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The development of new radiopharmaceuticals for the detection of hidden infection foci has great relevance for early detection and the selection of the correct treatment, particularly in immunosuppressed patients. In that sense, the labelling of antimicrobial peptides (AMPs) that are capable of binding specifically to the pathogenic microorganism which causes the infection, should provide a sufficiently specific agent, able to distinguish an infection from a sterile inflammation. Defensins are particularly interesting molecules with antimicrobial activity, the EcgDf1 defensin was identified from the genome of a Uruguayan native plant, Erythrina crista-galli, the 'Ceibo' tree. Our group has previously reported a synthetic biologically active short analogue EcgDf21 (ERFTGGHCRGFRRRCFCTKHC) successfully labelled with 99m Tc. Herein we present a shorter analogue which also preserves the γ-core domain, as a pharmacophore for a potential infection detection agent. This peptide was derivatized with the bifunctional chelating agent 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) through a lysine linker in the amino-terminal group (NOTA-KGHCRGFRRRC) and radiolabelled with 68 Ga ([ 68 Ga]Ga-NOTA-K-EcgDf1 (10) ). The [ 68 Ga]Ga-NOTA-K-EcgDf1 (10) labelling procedure rendered a product with high radiochemical purity and stability in the labelling milieu. The Log P value indicated that the complex has a hydrophilic behaviour, confirmed by the biodistribution profile. The [ 68 Ga]Ga-NOTA-K-EcgDf1 (10) complex demonstrated specific binding to cultures of Candida albicans and Aspergillus niger. Its biodistribution showed renal elimination and low accumulation in the rest of the body. It was possible to successfully differentiate sterile inflammation from infection by PET images in nude mice with a target/non-target ratio of 3.3 for C. albicans and 3.7 for A. niger, respectively., (© 2024 John Wiley & Sons Ltd.)

Candida albicans (C. albicans) is one of the most common fungi in the human body; it is an opportunistic pathogen and can cause candidiasis. Extracellular vesicles (EVs) derived from the host cells have a potentially protective effect against pathogens and can be developed as vaccine formulations. GW4869 can inhibit the production and release of EVs. Previous studies have indicated that GW4869 can alter the immune and inflammatory responses of the host. However, the effect of GW4869 on Candida infection and the anti-Candida response of the host has not been investigated. We evaluated the effect of GW4869 on C. albicans invasion, biofilm formation, and cellular damage in a murine model of oral candidiasis. In this study, C. albicans-infected mice were injected with or without GW4869. The results proven by macroscopic, microscopic, and ultramicroscopic methods showed that GW4869 treatment exacerbated the oral candidiasis of mice, promoted C. albicans invasion and biofilm formation, and aggravated oral mucosal inflammation and cellular ultrastructural damage. The results are beneficial in the further exploration of the immune mechanism of C. albicans infection.

Background Fungal infections pose a significant global health challenge. Despite their substantial impact, these ubiquitous fungi can become pathogenic but have not received adequate attention in public health, leading to infections that are often underestimated by the general public and healthcare professionals. Candida species and Cryptococcus species play a key role in these infections, with emerging multidrug resistance in Candida species posing considerable challenges. This study aimed to understand the prevalence of yeast and yeast-like infections, particularly in the COVID-19 era, and to assess the antifungal susceptibility pattern. Methodology A retrospective observational study was conducted at a rural tertiary care medical college in Maharashtra, India. Retrospective records of samples processed for fungal culture were analyzed in the microbiology department. Yeast identification and antifungal susceptibility were performed using the VITEK-2 automated system. Results Among 95 fungal isolates, 86 (90.52%) were yeast isolates, primarily non-albicans Candida (NAC) species. Candida albicans accounted for 41 (47.67%) yeast isolates. In 14 isolates, NAC species were not identified by the VITEK-2 system up to the species level. Isolates from urine samples contributed the highest percentage of 61% (58) of yeast isolates. C. albicans showed high sensitivity to most antifungal agents. Other Candida species , such as Candida famata, Candida parapsilosis , and Candida guilliermondii , were sensitive to all antifungal agents. Candida auris showed complete resistance to amphotericin B and fluconazole but sensitivity to other agents. Mixed sensitivity patterns were observed in Candida ciferri and Candida lusitaniae , with some resistance to voriconazole, caspofungin, and micafungin. Conclusions This study shows the increasing prevalence of yeast and yeast-like infections, particularly NAC, during the COVID-19 era. Improved yeast identification and susceptibility testing are crucial for guiding the appropriate treatment and mitigating the impact of these infections, emphasizing the need for comprehensive future studies in this area., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shelke et al.)

Data-independent acquisition has seen breakthroughs that enable comprehensive proteome profiling using short gradients. As the proteome coverage continues to increase, the quality of the data generated becomes much more relevant. Using Spectronaut, we show that the default search parameters can be easily optimized to minimize the occurrence of false positives across different samples. Using an immunological infection model system to demonstrate the impact of adjusting search settings, we analyzed Mus musculus macrophages and compared their proteome to macrophages spiked with Candida albicans . This experimental system enabled the identification of "false positives" as Candida albicans peptides and proteins should not be present in the Mus musculus -only samples. We show that adjusting the search parameters reduced "false positive" identifications by 89% at the peptide and protein level, thereby considerably increasing the quality of the data. We also show that these optimized parameters incurred a moderate cost, only reducing the overall number of "true positive" identifications across each biological replicate by <6.7% at both the peptide and protein level. We believe the value of our updated search parameters extends beyond a two-organism analysis and would be of great value to any DIA experiment analyzing heterogeneous populations of cell types or tissues.

Candida albicans infections are widespread in people and cause cutaneous and systemic infections. Optimisation of garlic mustard oil macerate (GMM) based on antifungal activity against C. albicans was done using agar diffusion method. Upon vapour diffusion assay, the volatile organic compounds of both GMM and MO were found to eradicate C. albicans . During agar diffusion, MO did not inhibit fungal growth, while undiluted GMM oil demonstrated a 26.33 ± 0.33 mm zone of inhibition. The minimum inhibitory concentration and minimum fungicidal concentration against C. albicans were 12.5%, v/v of GMM oil and 25%, v/v of GMM oil, respectively. Scanning electron microscopy analysis showed cell membrane disintegration of fungal cells by 50%, v/v of GMM oil, and MO caused no cell wall damage. In-silico analysis revealed strong binding affinity of sinigrin, ajoene, dithiin with N-myristoyltransferase. In conclusion, the optimised GMM preparation can be a potential antifungal agent against tropical C. albicans infections.

Early childhood caries (ECC), a severe form of caries due to cross-kingdom interaction of Candida albicans and Streptococcus mutans , is a serious childhood dental disease that affects majority of the children with poor background. The present study investigated the anti-infective potential of thymol against C. albicans and S. mutans dual species for the management of ECC. Thymol, a plant derivative of the monoterpene group, has been well known for its numerous biological activities. Thymol at 300 μg/ml concentration completely arrested growth and proliferation of dual species of C. albicans and S. mutans. Rapid killing efficacy of pathogens, within a span of 2 min, was observed in the time kill assay. In addition, at sub-inhibitory concentrations, thymol effectively diminished the biofilm formation and virulence of both C. albicans and S. mutans such as yeast-to-hyphal transition, hyphal-to-yeast transition, filamentation, and acidogenicity and acidurity, respectively, in single and dual species state. qPCR analysis was consistent with virulence assays. Also, through the invertebrate model system Galleria mellonella , in vivo toxicity and efficacy of the phytocompound was assessed, and it was found that no significant toxic effect was observed. Moreover, thymol was found to be proficient in diminishing the infection under single and dual state in in vivo condition. Overall, the results from the present study illustrate the anti-infective potential of thymol against the ECC-causing dual species, C. albicans and S. mutans , and the applicability of thymol in medicated dentifrice formulation. [ABSTRACT FROM AUTHOR]

This study aims to determine the frequency of fungal causative agents for cervicitis in cows. The vaginal swabs were taken from (20 cows), which suffered from cervicitis after parturition; the swabs were cultured on chrome agar and Sabouraud dextrose agar at ( 25 ± 2°C) in an incubator for 5-7 days and lactophenol cotton blue dye was used for identification of the fungal components. The results appear that the frequency of positive fungal samples was (7/20) 35%. Candida albicans was isolated from (5/20), 25%. Aspergillus flavus (2/20), 10% thirteen samples were given a negative result for fungal infection (13/20), 65%. [ABSTRACT FROM AUTHOR]

In the present work, we have studied the inactivation of Candida albicans (C. albicans) and lemon (Citrus limon) spoilage fungi using plasma activated water (PAW). Air and N2 are used as plasma forming gases for PAW preparation. Optical emission spectroscopy is used to determine various active radicals and species present in the air and N2 plasma. The present study shows the changes in physicochemical properties and reactive oxygen–nitrogen species formed in PAW. Furthermore, the fungicidal efficacy of PAW is investigated on C. albicans. The role of oxidizing potential of PAW and PAW treatment time with fungi (C. albicans and Citrus limon spoilage fungi) is investigated in the present work. Results showed high oxidizing PAW can achieve 6 + log10 CFU ml−1 reduction in fungi even with low treatment time. Morphology analysis by HR-SEM, leaked nucleic acids and protein measurement by UV–visible spectroscopy, and PI binding red fluorescence of cells showed PAW treatment with C. albicans damaged the membrane of cells due to which leakage of extracellular materials occurred that led to cells death. The present study also reveals the long-term fungicidal efficacy of PAW on C. albicans and Citrus limon spoilage fungi. [ABSTRACT FROM AUTHOR]

The objective of this article is the creation and investigation of bifunctional suppositories that are endowed with antifungal and probiotic properties intended for the treatment of vulvovaginal candidiasis (VVC) and colonization of the vaginal cavity by powerful lactobacilli. Freeze-dried Lactobacillus delbrueckii MH10 was used as a probiotic, which is an active producer of H2O2 isolated from a healthy woman's vagina. Hydrophilic PEG 4000/400, amphiphilic Suppocire AP, and lipophilic Novata ABPH bases were used for the preparation of vaginal suppositories and each included 80 mg terconazole and 25 mg (∼109 CFU) lactobacilli. The release kinetic of active agents from suppositories was studied using the British Pharmacopeia's basket dissolution method, and the physicochemical properties were studied using known methods. Bioadhesion of suppositories was evaluated by flow rate from polyacrylamide substrate inclined at 60°. Antagonism of lactobacillus against fungi was studied using the disk diffusion method and joint cultivation in simulated vaginal fluid. The release rate of active ingredients from the suppositories was PEG 4000/400 > Suppocire AP > Novata ABPH in decreasing order. Suppositories made of Suppocire AP possessed higher adhesion ability to artificial mucosa and longer shelf life. It was revealed that during joint cultivation L. delbrueckii MH10 kills more than 90% of C. albicans population. Due to its physicochemical, biopharmaceutical, and bioadhesive properties, the base Suppocire AP is preferable for manufacturing vaginal bifunctional suppositories. Lactobacilli kill C. albicans by coaggregating and direct releasing hydrogen peroxide onto target cells. [ABSTRACT FROM AUTHOR]

Early childhood caries (ECC), a severe form of caries due to cross-kingdom interaction of Candida albicans and Streptococcus mutans, is a serious childhood dental disease that affects majority of the children with poor background. The present study investigated the anti-infective potential of thymol against C. albicans and S. mutans dual species for the management of ECC. Thymol, a plant derivative of the monoterpene group, has been well known for its numerous biological activities. Thymol at 300 μg/ml concentration completely arrested growth and proliferation of dual species of C. albicans and S. mutans. Rapid killing efficacy of pathogens, within a span of 2 min, was observed in the time kill assay. In addition, at sub-inhibitory concentrations, thymol effectively diminished the biofilm formation and virulence of both C. albicans and S. mutans such as yeast-to-hyphal transition, hyphal-to-yeast transition, filamentation, and acidogenicity and acidurity, respectively, in single and dual species state. qPCR analysis was consistent with virulence assays. Also, through the invertebrate model system Galleria mellonella, in vivo toxicity and efficacy of the phytocompound was assessed, and it was found that no significant toxic effect was observed. Moreover, thymol was found to be proficient in diminishing the infection under single and dual state in in vivo condition. Overall, the results from the present study illustrate the anti-infective potential of thymol against the ECC-causing dual species, C. albicans and S. mutans, and the applicability of thymol in medicated dentifrice formulation.

ABSTRACT Candida albicans is a commensal fungus that causes systemic infections in immunosuppressed patients. In order to deal with the changing environment during commensalism or infection, C. albicans must reprogram its proteome. Characterizing the stress-induced changes in the proteome that C. albicans uses to survive should be very useful in the development of new antifungal drugs. We studied the C. albicans global proteome after exposure to hydrogen peroxide (H2O2) and acetic acid (AA), using a data-independent acquisition mass spectrometry (DIA-MS) strategy. More than 2,000 C. albicans proteins were quantified using an ion library previously constructed using data-dependent acquisition mass spectrometry (DDA-MS). C. albicans responded to treatment with H2O2 with an increase in the abundance of many proteins involved in the oxidative stress response, protein folding, and proteasome-dependent catabolism, which led to increased proteasome activity. The data revealed a previously unknown key role for Prn1, a protein similar to pirins, in the oxidative stress response. Treatment with AA resulted in a general decrease in the abundance of proteins involved in amino acid biosynthesis, protein folding, and rRNA processing. Almost all proteasome proteins declined, as did proteasome activity. Apoptosis was observed after treatment with H2O2 but not AA. A targeted proteomic study of 32 proteins related to apoptosis in yeast supported the results obtained by DIA-MS and allowed the creation of an efficient method to quantify relevant proteins after treatment with stressors (H2O2, AA, and amphotericin B). This approach also uncovered a main role for Oye32, an oxidoreductase, suggesting this protein as a possible apoptotic marker common to many stressors. IMPORTANCE Fungal infections are a worldwide health problem, especially in immunocompromised patients and patients with chronic disorders. Invasive candidiasis, caused mainly by C. albicans, is among the most common fungal diseases. Despite the existence of treatments to combat candidiasis, the spectrum of drugs available is limited. For the discovery of new drug targets, it is essential to know the pathogen response to different stress conditions. Our study provides a global vision of proteomic remodeling in C. albicans after exposure to different agents, such as hydrogen peroxide, acetic acid, and amphotericin B, that can cause apoptotic cell death. These results revealed the significance of many proteins related to oxidative stress response and proteasome activity, among others. Of note, the discovery of Prn1 as a key protein in the defense against oxidative stress as well the increase in the abundance of Oye32 protein when apoptotic process occurred point them out as possible drug targets.

The biofilm formation of C. albicans represents a major virulence factor during candidiasis. Biofilm-mediated drug resistance has necessitated the search for a new antifungal treatment strategy. In our previous study, a novel antimicrobial peptide named AMP-17 derived from Musca domestica was confirmed to have significant antifungal activity and suppress hyphal growth greatly in C. albicans. In the current work, we aimed to investigate the antibiofilm property of AMP-17 in C. albicans and explore the underlying mechanism. An antifungal susceptibility assay showed that AMP-17 exerted a strong inhibitory efficacy on both biofilm formation and preformed biofilms in C. albicans. Furthermore, AMP-17 was found to block the yeast-to-hypha transition and inhibit the adhesion of biofilm cells with a reduction in cellular surface hydrophobicity. A morphological analysis revealed that AMP-17 indeed suppressed typical biofilm formation and damaged the structures of the preformed biofilm. The RNA-seq showed that the MAPK pathway, biosynthesis of antibiotics, and essential components of the cell were mainly enriched in the biofilm-forming stage, while the citrate cycle (TCA cycle), phenylamine metabolism, and propanoate metabolism were enriched after the biofilm matured. Moreover, the co-expressed DEGs in the two pairwise comparisons highlighted the terms of transmembrane transporter activity, regulation of filamentation, and biofilm formation as important roles in the antibiofilm effect of AMP-17. Additionally, qRT-PCR confirmed that the level of the genes involved in cell adhesion, filamentous growth, MAPK, biofilm matrix, and cell dispersal was correspondingly altered after AMP-17 treatment. Overall, our findings reveal the underlying antibiofilm mechanisms of AMPs in C. albicans, providing an interesting perspective for the development of effective antifungal agents with antibiofilm efficacy in Candida spp.

Candida albicans (C. albicans) is the most common fungal pathogen causing recurrent mucosal and life-threatening systemic infections. The ability to switch from yeast to hyphae and produce biofilm are the key virulence determinants of this fungus. In fact, Candida biofilms on medical devices represent the major risk factor for nosocomial bloodstream infections. Novel antifungal strategies are required given the severity of systemic candidiasis, especially in immunocompromised patients, and the lack of effective anti-biofilm treatments. Retinoids have gained attention recently due to their antifungal properties. Material and methods: The present study aimed at evaluating the in vitro effects of different concentrations (300 to 18.75 µg/mL) of All-trans Retinoic Acid (ATRA), a vitamin A metabolite, on Candida growth and biofilm formation. Results: ATRA completely inhibited the fungal growth, by acting as both fungicidal (at 300 µg/mL) and fungistatic (at 150 µg/mL) agent. Furthermore, ATRA was found to negatively affect Candida biofilm formation in terms of biomass, metabolic activity and morphology, in a dose-dependent manner, and intriguingly, its efficacy was as that of amphotericin B (AmB) (2–0.12 μg/mL). Additionally, transmission electron microscopy (TEM) analysis showed that at 300 μg/mL ATRA induced plasma membrane damage in Candida cells, confirming its direct toxic effect against the fungus. Conclusion: Altogether, the results suggest that ATRA has a potential for novel antifungal strategies aimed at preventing and controlling biofilm-associated Candida infections.

Circulatory inflammatory proteins play a significant role in anti-Candida host immune defence. However, little is known about the genetic variation that contributes to the variability of inflammatory responses in response to C. albicans. To systematically characterize inflammatory responses in Candida infection, we profiled 91 circulatory inflammatory proteins in peripheral blood mononuclear cells (PBMCs) stimulated with C. albicans yeast isolated from 378 individuals of European origin from the 500 Functional Genomics (500FG) cohort of the Human Functional Genomics Project (HFGP) and Lifelines Deep cohort. To identify the genetic factors that determine variation in inflammatory protein responses, we correlated genome-wide single nucleotide polymorphism (SNP) genotypes with protein abundance (protein quantitative trait loci, pQTLs) produced by the Candida-stimulated PBMCs. Furthermore, we investigated whether differences in survival of candidaemia patients can be explained by modulating levels of inflammatory proteins. We identified five genome-wide significant pQTLs that modulate IL-8, MCP-2, MMP-1, and CCL3 in response to C. albicans. In addition, our genetic analysis suggested that GADD45G from rs10114707 locus that reached genome-wide significance could be a potential core gene that regulates a cytokine network upon Candida infection. Last but not least, we observed that a trans-pQTL marked from SNP rs7651677 at chromosome 3 that influences urokinase plasminogen activator (uPA) is strongly associated with patient survival (Psurvival = 3.52 x 10-5, OR 3). Overall, our genetic analysis showed that genetic variation determines the abundance of circulatory proteins in response to Candida infection.

Vulvovaginal candidiasis (VVC) is a symptomatic inflammation of the vagina mainly caused by C. albicans. Other species, such as C. parapsilosis, C. glabrata, C. tropicalis, and C. krusei, are mainly associated to the recurrent form of the disease (RVVC), although with a lower frequency. In its yeast form, C. albicans is tolerated by the vaginal epithelium, but switching to the invasive hyphal form, co-regulated with the expression of genes encoding virulence factors such as secreted aspartyl proteases (Sap) and candidalysin, allows for tissue damage. Vaginal epithelial cells play an important role by impairing C. albicans tissue invasion through several mechanisms such as epithelial shedding, secretion of mucin and strong interepithelial cell connections. However, morphotype switching coupled to increasing of the fungal burden can overcome the tolerance threshold and trigger an intense inflammatory response. Pathological inflammation is believed to be facilitated by an altered vaginal microbiome, i.e., Lactobacillus dysbiosis. Notwithstanding the damage caused by the fungus itself, the host response to the fungus plays an important role in the onset of VVC, exacerbating fungal-mediated damage. This response can be triggered by host PRR-fungal PAMP interaction and other more complex mechanisms (i.e., Sap-mediated NLRP3 activation and candidalysin), ultimately leading to strong neutrophil recruitment. However, recruited neutrophils appear to be ineffective at reducing fungal burden and invasion; therefore, they seem to contribute more to the symptoms associated with vaginitis than to protection against the disease. Recently, two aspects of the vulvovaginal environment have been found to associate with VVC and induce neutrophil anergy in vitro: perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) and heparan sulfate. Interestingly, CAGTA antibodies have also been found with higher frequency in VVC as compared to asymptomatic colonized women. This review highlights and discusses recent advances on understanding the VVC pathogenesis mechanisms as well as the role of host defenses during the disease.

Circulatory inflammatory proteins play a significant role in anti- Candida host immune defence. However, little is known about the genetic variation that contributes to the variability of inflammatory responses in response to C. albicans. To systematically characterize inflammatory responses in Candida infection, we profiled 91 circulatory inflammatory proteins in peripheral blood mononuclear cells (PBMCs) stimulated with C. albicans yeast isolated from 378 individuals of European origin from the 500 Functional Genomics (500FG) cohort of the Human Functional Genomics Project (HFGP) and Lifelines Deep cohort. To identify the genetic factors that determine variation in inflammatory protein responses, we correlated genome-wide single nucleotide polymorphism (SNP) genotypes with protein abundance (protein quantitative trait loci, pQTLs) produced by the Candida -stimulated PBMCs. Furthermore, we investigated whether differences in survival of candidaemia patients can be explained by modulating levels of inflammatory proteins. We identified five genome-wide significant pQTLs that modulate IL-8, MCP-2, MMP-1, and CCL3 in response to C. albicans. In addition, our genetic analysis suggested that GADD45G from rs10114707 locus that reached genome-wide significance could be a potential core gene that regulates a cytokine network upon Candida infection. Last but not least, we observed that a trans-pQTL marked from SNP rs7651677 at chromosome 3 that influences urokinase plasminogen activator (uPA) is strongly associated with patient survival (P survival = 3.52 x 10-5, OR 3). Overall, our genetic analysis showed that genetic variation determines the abundance of circulatory proteins in response to Candida infection. [ABSTRACT FROM AUTHOR]

Lactoferricin (Lfcin) is an amphipathic, cationic peptide derived from proteolytic cleavage of the N-lobe of lactoferrin (Lf). Lfcin and its derivatives possess broad-spectrum antibacterial and antifungal activities. However, unlike their antibacterial functions, the modes of action of Lfcin and its derivatives against pathogenic fungi are less well understood. In this study, the mechanisms of LfcinB15, a derivative of bovine Lfcin, against Candida albicans were, therefore, extensively investigated. LfcinB15 exhibited inhibitory activity against planktonic cells, biofilm cells, and clinical isolates of C. albicans and non-albicans Candida species. We further demonstrated that LfcinB15 is localized on the cell surface and vacuoles of C. albicans cells. Moreover, LfcinB15 uses several different methods to kill C. albicans, including disturbing the cell membrane, inducing reactive oxygen species (ROS) generation, and causing mitochondrial dysfunction. Finally, the Hog1 and Mkc1 mitogen-activated protein kinases were both activated in C. albicans cells in response to LfcinB15. These findings help us to obtain more insight into the complex mechanisms used by LfcinB15 and other Lfcin-derived peptides to fight fungal pathogens. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Education & Science is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Candida albicans undergoes a morphological yeast-to-hyphal transition during infection, which plays a significant role in its pathogenesis. The filamentous morphology of the hyphal form has been identified as a virulence factor as it facilitates surface adherence, intertwining with biofilm, invasion, and damage to host tissues and organs. Hence, inhibition of filamentation in addition to biofilm formation is considered a viable strategy against C. albicans infections. Furthermore, a good understanding of the signaling pathways involved in response to environmental cues driving hyphal growth is also critical to an understanding of C. albicans pathogenicity and to develop novel therapies. In this review, first the clinical significance and transcriptional control of C. albicans hyphal morphogenesis are addressed. Then, various strategies employed to suppress filamentation, prevent biofilm formation, and reduce virulence are discussed. These strategies include the inhibition of C. albicans filament formation using natural or synthetic compounds, and their combination with other agents or nanoformulations. [ABSTRACT FROM AUTHOR]

Introduction: It is important to distinguish infecting strains of Candida albicans because isolates of Candida species vary widely, both in their infection-causing capacity and in their sensitivity to antifungal agents. Material and method: Thus this study provides isolate candida and identification of isolates from the oral cavity and test the antimicrobial activity of Lactobacillus rhamnosus GG and their supernatants on the viability of Candida albicans isolates. The diagnosis was based on conventional methods, and genetic diagnosis was confirmed by PLC1 gene (PhosphoLipase C) amplification, the design primers were done by using the database of Bank of NCBI-Gene and online design, all isolates gives positive PCR products with molecular weight 459bp, Result: The results showed that Lactobacillus rhamnosus GG and their supernatants decreased the log cycles growth of all Candida albicans isolates with average (1.7 -2.1) logarithmic cycle for live cells and (1.28 -1.79) logarithmic cycle for Lactobacillus rhamnosus GG supernatants, Conclusion: Lactobacillus rhamnosus GG may be a suitable and effective alternative to treatment oral candidiasis free from side effects. [ABSTRACT FROM AUTHOR]

Copyright of Baghdad Science Journal is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Vulvovaginal candidiasis (VVC) is a symptomatic inflammation of the vagina mainly caused by C. albicans. Other species, such as C. parapsilosis , C. glabrata , C. tropicalis , and C. krusei , are mainly associated to the recurrent form of the disease (RVVC), although with a lower frequency. In its yeast form, C. albicans is tolerated by the vaginal epithelium, but switching to the invasive hyphal form, co-regulated with the expression of genes encoding virulence factors such as secreted aspartyl proteases (Sap) and candidalysin, allows for tissue damage. Vaginal epithelial cells play an important role by impairing C. albicans tissue invasion through several mechanisms such as epithelial shedding, secretion of mucin and strong interepithelial cell connections. However, morphotype switching coupled to increasing of the fungal burden can overcome the tolerance threshold and trigger an intense inflammatory response. Pathological inflammation is believed to be facilitated by an altered vaginal microbiome, i.e., Lactobacillus dysbiosis. Notwithstanding the damage caused by the fungus itself, the host response to the fungus plays an important role in the onset of VVC, exacerbating fungal-mediated damage. This response can be triggered by host PRR-fungal PAMP interaction and other more complex mechanisms (i.e., Sap-mediated NLRP3 activation and candidalysin), ultimately leading to strong neutrophil recruitment. However, recruited neutrophils appear to be ineffective at reducing fungal burden and invasion; therefore, they seem to contribute more to the symptoms associated with vaginitis than to protection against the disease. Recently, two aspects of the vulvovaginal environment have been found to associate with VVC and induce neutrophil anergy in vitro : perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) and heparan sulfate. Interestingly, CAGTA antibodies have also been found with higher frequency in VVC as compared to asymptomatic colonized women. This review highlights and discusses recent advances on understanding the VVC pathogenesis mechanisms as well as the role of host defenses during the disease. [ABSTRACT FROM AUTHOR]

Candida albicans is one of the most common clinical pathogenic microorganisms and it is becoming a serious health threat, particularly to immunocompromised populations. Drug resistance of Candida species has also frequently emerged, and combination therapy for fungal infections has attracted considerable attention. In this study, we established the Qinling Mountains myxobacterial secondary metabolites library and a synergic assay in combination with ketoconazole against C. albicans was introduced for metabolites screening. Two active compounds with synergic anticandidal activities were obtained, which were identified as trans‐resveratrol and cis‐resveratrol. According to our study, resveratrol can reduce the dosage to 1/64 of ketoconazole as well as itraconazole. Furthermore, synergistic anticandidal activity of resveratrol combined with azoles was verified against a panel of clinical C. albicans isolates, and the combination strategy enhanced the azoles susceptibility of three fluconazole‐resistant isolates. These findings suggest that resveratrol enhances the efficacy of azoles and provides a promising application in therapy of C. albicans infection. [ABSTRACT FROM AUTHOR]

Apple vinegar has many uses that include burn and wound healing and as an antimicrobial agent against different microorganisms, but not as a solvent. Therefore, this study aimed to use commercial apple vinegar as solvent to the plants of roselle (Hibiscus sabdariffa), green tea (Camellia sinensis), and clove (Syzygium aromaticum). The effects of apple-vinegar extracts of these plants were compared with those of aqueous and ethanolic extracts against biofilm formation by Candida genus. Clove vinegar extract demonstrated antibiofilm activity against C. albicans, alone (2.4907± 0.382) or in combination with the antifungal agents fluconazole (1.689±0.33), nystatine (1.941±0.64), and clotrimazole (2.0353±0.71819). These plant extracts possessed a variable number of antimicrobial compounds, as tested by the HLPC technique. Therefore, apple vinegar was the most efficient solvent, in comparison with the other solvents used in this study, to obtain some phytochemical compounds from the tested plants that have antibiofilm activity against C. albicans. [ABSTRACT FROM AUTHOR]

[Display omitted] • The Cu-doped Ni-Co nanoferrites were synthesized via the green synthesis method. • XRD confirmed the single-phase formation with an average crystalline size of 22 nm. • FTIR spectra confirmed the functional groups at octahedral and tetrahedral sites. • The hysteresis curve depicted a specific saturation magnetization of 36.24 emu/g. • The antimicrobial studies indicated a good inhibition (0.24 O.D. for x = 0.6) against the C. albicans cells. • Low dielectric loss tangent values in the range (4.34–0.38) were observed. To investigate the antimicrobial studies against the C. albicans fungi, copper substituted Ni-Co nanoferrites were synthesized using the green synthesis process. Structural studies were evaluated using the X-Ray Diffraction pattern with 22 nm of average crystallite size. The Williamson Hall (W-H) plot for all the samples revealed a tensile strain. From the FTIR (Fourier Transform Infrared) spectra, the high frequency band was observed at 523.17 cm−1 while at 416.79 cm−1 a lower frequency band was observed. Magnetic studies were undertaken using vibrating sample magnetometer and saturation magnetization was observed to vary from 36.24 emu/g to 12.86 emu/g and a squareness ratio less than 0.5 was observed. Hence, it is confirmed from the magnetic studies that these ferrites can be used for storage device applications. From the dielectric studies, the value of the real part of dielectric constant was found to vary from 99.93 to 35.00. Similarly, dielectric loss (tan δ) also decreased with an increasing frequency from 4.34 to 0.38. The antimicrobial studies show a good inhibition (0.24 optical density for x = 0.6) against the C. albicans cells. Therefore, these Ni-Co nanoferrites can be utilized in high frequency applications as well as against the fungi Candida albicans. [ABSTRACT FROM AUTHOR]

Amaç: Bu retrospektif çalışmada premalign ve malign lezyonlu ile sağlıklı bireylere ait doku örneklerindeki Candida albicans, Candida kruseii, Candida parapsilosis, Candida tropicalis ve Candida glabrata türlerinin belirlenmesi amaçlanmıştır. Gereç ve Yöntem: Çalışmaya oral premalign veya malign lezyon şüphesi nedeniyle biyopsi uygulanmış doku örnekleri dahil edildi. Örnekler histolojik özelliklerine göre sağlıklı (n=20), displazi (n=20), karsinoma in-situ (n=20) ve skuamoz hücreli karsinom (SHK) (n=20) olmak üzere 4 gruba ayrıldı. DNA izolasyonunun ardından Candida türlerine ait DNA örneklerinin miktar ve saflık kontrolleri gerçekleştirildi. Kantitatif ölçümler için Real-Time PCR (LightCycler 96, Almanya) kullanıldı ve standart eğriler hesaplandı. Veriler Mann-Whitney ve Wilcoxon Signed Ranks testleri ile değerlendirildi (P0.05). Farklı Candida türlerinin gruplar içerisindeki seviyeleri incelendiğinde; sağlıklı örneklerde C. glabrata (103DNA/50 mg), displazi grubunda C. parapsilosis (104DNA/50 mg), karsinoma in-situ grubunda C. tropicalis-C. kruseii (103DNA/50 mg), SHK grubunda ise C. kruseii’nin (103DNA/50 mg) en fazla sayıda gözlenen Candida türü olduğu belirlendi. Candida türlerinin gruplar içerisindeki dağılımı anlamlı değildi (P>0.05).Sonuç: Sağlıklı, displazik, karsinoma in situ ve skuamöz hücreli karsinoma doku örneklerinde Real-Time PCR yöntemiyle yapılan kantitatif değerlendirmede Candida türlerinin tüm gruplarda benzer oranda mevcut oldukları belirlendi.ANAHTAR KELİMELER Oral Candida, C. albicans, ağız kanseri, Real-Time PCR, moleküler analiz

Candidiasis is an infectious disease caused by the fungus Candida albicans. This study aims to determine the effect of patikan kebo (Euphorbia hirta) leaf extract in inhibiting the growth of C. albicans. This research is an experimental study which was compiled using a Completely Randomized Design (CRD) by giving Patikan Kebo (E. hirta) leaf extract in several concentrations, the concentrations of 40%, 45%, 50%, 55%, and 60% and controls (aquadest) and C. albicans mushroom with three repetitions. The parameters measured are the amount of inhibitory diameter formed around the paper discs in the 24 hour and 48 hour period. D ata obtained with three repetitions and observations of 24 hours and 48 hours showed that giving patikan kebo leaf extract in several types of concentration had an effect on inhibiting the growth and fungi of C . albicans. Furthermore, the data obtained were analyzed using analysis of variance (F-test) at the level of α 0.05 and continued using the Smallest Significant Difference (LSD) α 0.05 where the results showed that the giving of patikan kebo extract significantly affected the microbial growth test (C. albicans), where the higher the concentration of patikan kebo leaf extract, the greater the inhibition zone formed around the paper disk.

Background: Fungal infections are a health issue paradoxically fuelled by the developments in medical care. Objectives: Our study is an investigation on the correlation between the infection site and the genotypes of Candida albicans strains isolated from Romanian patients. Methods: A total number of 301 isolates from different clinical sites were investigated in terms of genotype determination. Results: The isolates were clustered in three groups according to their genotype: 55.81% showed genotype A, 14.62% genotype B, and 29.57% genotype C. Conclusions: No significant correlation was found between the genotype and the infection site, but a significant correlation was found between genotype C and isolates from HIV patients proving that C. albicans pathogenicity probably relies on factors related to the host.

Latar belakang: Kandidiasis vulvovaginalis (KVV) merupakan penyakit infeksi dengan gejala dan keluhan keradangan pada vulva dan vagina yang disebabkan oleh jamur spesies Candida. C. albicans merupakan spesies terbanyak penyebab KVV, tetapi kejadian yang disebabkan oleh spesies non-albicans tampak semakin meningkat dengan berbagai komplikasi yang ditimbulkannya. Tujuan: Mengevaluasi pola pergeseran spesies penyebab KVV untuk meningkatkan keberhasilan pengobatan pasien. Metode: Studi retrospektif dengan sumber data sekunder yang tersedia dari hasil penelitian KVV di Divisi Infeksi Menular Seksual (IMS) Unit Rawat Jalan (URJ) Kesehatan Kulit dan Kelamin RSUD Dr. Soetomo Surabaya periode tahun 1997 – 2017. Hasil: Sebanyak 7 penelitian mengenai KVV telah didapatkan dalam rentang waktu tersebut. Pasien KVV sebagian besar adalah wanita yang sudah menikah, usia seksual aktif, dan mengeluhkan adanya duh tubuh berwarna putih disertai rasa gatal pada kemaluan. Mayoritas C. albicans didapatkan pada penelitian tahun 1997, 2010, 2015, dan 2017, sebesar 100%, 52,8%, 71,4%, dan 62,1%, sedangkan mayoritas C. non-albicans pada penelitian tahun 2004, 2005, dan 2009, sebesar 65,2%, 52,6%, dan 52,9%. Kesimpulan: Penelitian ini telah menunjukkan pola pergeseran spesies penyebab KVV selama 20 tahun terakhir, yaitu dari dominasi C. albicans pada 1997, kemudian C. non-albicans pada tahun 2004, 2005, dan 2009, kembali lagi pada dominasi C. albicans yaitu pada tahun 2010, 2015, dan 2017.

Candida species are major fungal pathogens in humans. The aim of this study was to determine the prevalence of individual Candida species and their susceptibility to antifungal drugs among clinical isolates in a tertiary care hospital in Bangladesh. During a 10-month period in 2021, high vaginal swabs (HVSs), blood, and aural swabs were collected from 360 patients. From these specimens, Candida spp. was isolated from cultures on Sabouraud dextrose agar media, and phenotypic and genetic analyses were performed. A total of 109 isolates were recovered, and C. albicans accounted for 37%, being derived mostly from HVSs. Among non-albicans Candida (NAC), C. parapsilosis was the most frequent, followed by C. ciferrii, C. tropicalis, and C. glabrata. Three isolates from blood and two isolates from aural discharge were genetically identified as C. auris and Kodamaea ohmeri, respectively. NAC isolates were more resistant to fluconazole (overall rate, 29%) than C. albicans (10%). Candida isolates from blood showed 95% susceptibility to voriconazole and less susceptibility to fluconazole (67%). Two or three amino acid substitutions were detected in the ERG11 of two fluconazole-resistant C. albicans isolates. The present study is the first to reveal the prevalence of Candida species and their antifungal susceptibility in Bangladesh.

Candida albicans is a common fungal pathogen. Biofilm formation on various surfaces is an important determinant of C. albicans pathogenicity. Our previous results demonstrated the high potential of cannabidiol (CBD) to affect C. albicans biofilms. Based on these data, we investigated the possibility of incorporating CBD and/or triclosan (an antimicrobial agent that is widely utilized in dentistry) in a sustained-release varnish (SRV) (SRV-CBD, SRV-triclosan) to increase their pharmaceutical potential against C. albicans biofilm, as well as that of the mixture of the agents into SRV (SRV-CBD/triclosan). The study was conducted in a plastic model, on agar, and in an ex vivo tooth model. Our results demonstrated strong antibiofilm activity of SRV-CBD and SRV-triclosan against C. albicans in all tested models. Both formulations were able to inhibit biofilm formation and to remove mature fungal biofilm. In addition, SRV-CBD and SRV-triclosan altered C. albicans morphology. Finally, we observed a dramatic enhancement of antibiofilm activity when combined SRV-CBD/triclosan was applied. In conclusion, we propose that incorporation of CBD or triclosan into SRV is an effective strategy to fight fungal biofilms. Importantly, the data demonstrate that our CBD/triclosan varnish is safe, and is not cytotoxic for normal mammalian cells. Furthermore, we propose that CBD and triclosan being in mixture in SRV exhibit complementary antibiofilm activity, and thus can be explored for further development as a potential treatment against fungal infections.

As dramatically experienced in the recent world pandemic, viral, bacterial, fungal pathogens constitute very serious concerns in the global context of human health. Regarding this issue, the World Health Organization has promoted research studies that aim to develop new strategies using natural products. Although they are often competitive with synthetic pharmaceuticales in clinical performance, they lack their critical drawbacks, i.e., the environmental impact and the high economic costs of processing. In this paper, the isolation of a highly performant antibacterial and antifungal lipophilic natural mixture from leaves of savoy and white cabbages is proposed as successful preliminary results for the valorization of agricultural waste produced in cabbage cultivation. The fraction was chemically extracted from vegetables with diethyl ether and tested against two Candida species, as well as Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus reference strains. All the different fractions (active and not active) were chemically characterized by vibrational FT-IR spectroscopy and GC-MS analyses. The extracts showed high growth-inhibition performance on pathogens, thus demonstrating strong application potential. We think that this work, despite being at a preliminary stage, is very promising, both from pharmaceutical and industrial points of view, and can be proposed as a proof of concept for the recovery of agricultural production wastes.

Candida albicans is the most dominant and prevalent cause of fungal infections in humans. Azoles are considered as first-line drugs for the treatment of these infections. However, their prolonged and insistent use has led to multidrug resistance and treatment failures. To overcome this, modification or derivatization of the azole ring has led to the development of new and effective antifungal molecules. In a previous study, we reported on the development of new triazole-based molecules as potential antifungal agents against Candida auris. In this study, the most potent molecules from the previous study were docked and simulated with lanosterol 14-alpha demethylase enzyme. These compounds were further evaluated for in vitro susceptibility testing against C. albicans. In silico results revealed favorable structural dynamics of the compounds, implying that the compounds would be able to effectively bind to the target enzyme, which was further manifested by the strong interaction of the test compounds with the amino acid residues of the target enzyme. In vitro studies targeting quantification of ergosterol content revealed that pta1 was the most active compound and inhibited ergosterol production by >90% in both drug-susceptible and resistant C. albicans isolates. Furthermore, RT-qPCR results revealed downregulation of ERG11 gene when C. albicans cells were treated with the test compound, which aligns with the decreased ergosterol content. In addition, the active triazole derivatives were also found to be potent inhibitors of biofilm formation. Both in silico and in vitro results indicate that these triazole derivatives have the potential to be taken to the next level of antifungal drug development.

Oral candidiasis (OC) is a fungal infection caused by an opportunistic fungi Candida albicans, which is found in the normal flora of healthy people. In this study, we examined the anti-candidal effect of green synthesized silver nanoparticles using leaf extract of Erodium glaucophyllum (EG-AgNPs) against C. albicans in vitro and in vivo. EG-AgNPs were synthesized for the first time using E. glaucophyllum extract and characterized by imaging (transmission electron microscopy (TEM), UV-VIS spectroscopy, zeta potential, X-ray diffraction (XRD), Energy dispersive x-ray analysis (EDX), and Fourier transform infrared spectroscopy (FTIR). A mouse model of OC was used for in vivo study. The agar well diffusion method showed the anti-candidal activity of EG-AgNPs against C. albicans with MIC 50 µg/mL. EG-AgNPs inhibited the dimorphic transition of C. albicans and suppressed the formation of biofilm by 56.36% and 52%, respectively. Additionally, EG-AgNPs significantly inhibited the production of phospholipases and proteinases by 30% and 45%, respectively. EG-AgNPs cause cytoplasm disintegration and deterioration of cell wall as imaged by SEM and TEM. Interestingly, EG-AgNPs did not display any cytotoxicity on the human gingival fibroblast-1 HGF-1 cell line at MIC concentrations. Topical treatment of the tongue of the OC mouse model with EG-AgNPs showed significant reduction in candidal tissue invasion, less inflammatory changes, and no tissue modification, in association with marked low scare and hyphal counts as compared to control group. In conclusion, our data demonstrated the potent inhibitory action of EG-AgNPs on the growth and morphogenesis of C. albicans in vitro and in vivo. Thus, EG-AgNPs represent a novel plausible therapeutic approach for treatment of OC.

Natamycin (NAT) is the drug of choice for the treatment of fungal keratitis (FK). However, its inherent shortcomings, such as poor solubility, high dosing frequency, and long treatment cycle, need to be urgently addressed by designing a new delivery to widen its clinical utility. Growing research has confirmed that clotrimazole (CLZ) plays a significant role in fungal growth inhibition. Hence, coaxial electrospray (CO-ES) technology is used herein to prepare nano-systems with an average hydrodynamic particle size of 309-406 nm for the co-delivery of NAT and CLZ in chitosan (CTS) and poly(lactic-co-glycolic acid) (PLGA). The resulting NAT/CLZ@CTS/PLGA formulations were characterized by a transmission electron microscope (TEM) and in vitro release test. The results show that the formulations had obvious core-shell structures, uniform particle distribution, and also can sustain the release of drugs over 36 h. Furthermore, in vitro hemolysis, in vivo corneal irritation test, local allergenic test, and antifungal activity analyses are performed to evaluate the safety and efficiency of the formulations. Thus, good biosafety along with a significant anti-candidiasis effect are found in the NAT/CLZ@CTS/PLGA nanoparticles (NPs). Taken together, the results suggest that this design may provide a promising drug delivery system and a new option for the treatment of FK.

Candida albicans (C. albicans) is a fungal pathogen that is difficult to cure clinically due to lack of effective antifungal agents with low toxicity. In this study, iturin, a cyclic peptide having wide antifungal spectrum, was used to synthesize nanosilver particles (AgNPs), and a complex of iturin-AgNPs was formed. The antifungal activity of iturin-AgNPs against C. albicans and its mechanisms were tested in vitro. Iturin-AgNPs were also loaded in chitosan (CS) composite dressing and applied to skin wound healing in mice. As results, iturin-AgNPs showed excellent antifungal activity with the minimum inhibitory concentrations (MIC) of 1.25, 2.5, and 5 μg/mL at C. albicans concentrations of 1×105, 1×106, and 1×107 CFU/mL, respectively. The MIC value still kept at 2.5 μg/mL against C. albicans (105 CFU/mL) after 15 regeneration, showing less induction of drug resistance to the pathogenic fungus. The antifungal mechanisms of iturin-AgNPs against C. albicans were identified as the increase of membrane permeability, damage of cell membrane integrity, and leakage of cellular protein and nucleic acids. No toxicity was found for iturin-AgNPs to HaCaT cells at concentrations of lower than 10 μg/mL. In wound healing application, iturin-AgNP CS composite dressing significantly accelerated the healing of C. albicans infected skin wounds at the early 10 days. In conclusion, iturin-AgNPs were developed as an efficient antifungal agent against C. albicans in vitro and in vivo and showed potential application in wound healing promotion. [ABSTRACT FROM AUTHOR]

A variety of Candida spp. as the most common fungi in the human body can normally be found in the vagina competing with other microbotes. Their presence is influenced by a variety of conditions in the vaginal environment. The proliferation of Candida spp. in the vagina under specific conditions can result in a fungal disease known as vaginal candidiasis. More than 17 species of Candida out of 200 members of this genus are capable of causing diseases within the human body. Estrogen, along with other steroidal hormones, has been shown to have direct multifunctional effects on various pathogenic microorganisms by numerous activities. Its production as well as other factors such as disturbance of microbial balance and immune activity may alter the vaginal physical environment and promote the development of vaginal fungal infection. The vaginal functions can be affected by the level of circulation of estrogens in the blood according to the stage of the menstrual cycle in women. It also has many other functional actions on the vaginal structure. Estrogen and several other factors play an important role in determining the vaginal content of Candida species. Its effect could be a direct action on the cells of Candida or through an indirect effect on the immunity defenses of the vagina. [ABSTRACT FROM AUTHOR]

Introduction: Denture stomatitis is considered one of the most common oral diseases associated with patients wearing dentures. Smokers have an increased incidence of denture stomatitis. Candida albicans has been associated with poor oral hygiene, combined with other factors like ill-fitting dentures, increased age of dentures and mucosal trauma, leading to C. albicans infections and denture stomatitis. Nicotine increases C. albicans biofilm formation. Nystatin h as been used for decades in the treatment of oral fungal infection. The primary aim of this study was to investigate whether nystatin limits the effects of nicotine on increasing biofilm formation and metabolic activity of C. albicans on acrylie resin denture materials. Materials and methods: Standardized denture acrylic resin (PMMA) specimens (66 specimens) incubated with C. albicans were exposed to nicotine at different concentrations (0, 2, 4, 8, 16 mg/ml) for 24 hours, in 6-well culture plates with 0.8 mg/ml of nystatin. The viability of treated C. albicans was measured using spiral plating. Results and discussion: The viability of C. albicans increased concomitantly with increasing concentrations of nicotine, particularly at 2 and 4 mg/ml, respectively. Concentrations of nicotine above this resulted in an inhibitory effect on C. albicans viability. Addition of nystatin at 0.8 mg/ml decreased C. albicans viability, compared to 4 mg/ml of nicotine alone. Conclusions: Nicotine at 4 mg/ml increases the viability of C. albicans on denture base material, while nystatin was able to limit the negative effect of nicotine at different concentrations. [ABSTRACT FROM AUTHOR]

Background: Gutta-percha cones used directly from the manufacturer's sealed packs harbour micro-organisms. During clinical use, the chances of contamination of gutta-percha increases. Hence, disinfection of gutta-percha cones before use is essential to prevent canal recontamination.Aim: To evaluate the antimicrobial efficacy of babul against chemical disinfectants, and its effectiveness in disinfecting gutta-percha cones.Materials and Methods: The extract of babul was used to assess its antimicrobial activity against E-faecalis, S. aureus and C. albicans using the agar diffusion method. A total of 120 cones acquired from freshly opened manufacturers' pack were cut into three equal parts and divided into group I which was directly placed into a nutrient broth, group II was clinically contaminated with gloves for 30 s and placed into a nutrient broth, and the third part was clinically contaminated with gloves and decontaminated for 5 min using the experimental disinfectants to check for the presence of turbidity.Statistical Analysis: The data were analysed by an Unpaired t-test and Chi-square test at a significance level of P < 0.05 using software SPSS 20.Results: Two percent chlorhexidine showed maximum antibacterial action against E. faecalis and S. aureus followed by babul extract. It was also found more efficacious in decontaminating gutta-percha cones followed by babul and 3% sodium hypochlorite in 5 min.Conclusion: Babul herbal extract is indeed effective in decontaminating gutta-percha cones and is a better alternative to chemical disinfectants. [ABSTRACT FROM AUTHOR]

Candida albicans is a member of pathogens with potential drug resistance threat that needs novel chemotherapeutic strategies. Considering the multifarious biological activities including bioenhancer activity, anti- Candida potential of piperine was evaluated against planktonic/biofilm and hyphal growth of C. albicans alone or in combination as a synergistic agent with fluconazole. Piperine inhibits planktonic growth at or less than 15 μg/ml, hyphae induction at 5 μg/ml concentration, and exhibits stage-dependent activity against biofilm growth of a fluconazole-resistant strain of C. albicans (ATCC10231). Though piperine couldn't kill inoculum completely at minimum inhibitory concentration (MIC), it is fungicidal at higher concentrations, as shown in apoptosis assay. FIC index values indicate that piperine exhibits excellent synergistic activity with fluconazole against planktonic (0.123) and biofilm (0.215) growth of an FLC resistant strain. Mode of anti- Candida activity was studied by identifying piperine responsive proteins wherein the abundance of 25 proteins involved in stress response, signal transduction and cell cycle were modulated (22 up and 3 down-regulated) significantly in response to piperine (MIC50). Modulation of the proteins involved suggests that piperine affects membrane integrity leading to oxidative stress followed by cell cycle arrest and apoptosis in C. albicans. Flow cytometry-based mitochondrial membrane potential (MMP), cell cycle and apoptosis assay, as well as real-time quantitative polymerase chain reaction analysis of selected genes, confirms piperine induced oxidative stress (TRR1), cell cycle arrest and apoptosis (CaMCA1). Based on our results, we conclude that piperine inhibits planktonic and difficult-to treat-biofilm growth of C. albicans by affecting membrane integrity thereby inducing oxidative stress and apoptosis. Lay Abstract Piperine inhibit Candida albicans growth (planktonic and biofilm) significantly in our study. Piperine exhibits excellent synergistic potential with fluconazole The proteome analysis suggests that piperine induced membrane damage leads to oxidative stress followed by cell cycle arrest and apoptosis. [ABSTRACT FROM AUTHOR]

PURPOSE. The purpose of this study is to compare the antibacterial activity of currently purchasable denture cleansers against Candida albicans. Materials and methods: This study used tablet-type denture cleansers, Polident®, Coolingdent® and Fittydent®, along with liquid denture cleansers, Hexamedine®, Listerine® and Apple vinegar®. The antibacterial activities of denture cleansers were evaluated based on the number of C. albicans and concentrations of the denture cleansers. Results. In the 0.5 × 106 cfu/® culture medium, the C. albicans' death rate of Polident® was significantly lower than those of Fittydent®, Hexamedine®, Listerine®, and Apple vinegar®(P <.05). In the 0.5 × 107 cfu/, the C. albicans' death rates of Polident® and Coolingdent® were significantly lower than those of Fittydent®, Hexamedine®, Listerine® and Apple vinegar®(P <.05). The C. albicans' death rates of Polident® and Coolingdent® were significantly decreased at 0.02 g and 0.01 g. The C. albicans' death rate of Fittydent® was significantly decreased at 0.005 g (P <.05). The C. albicans' death rate of Hexamedine® was significantly decreased at 1/16 dilution. The C. albicans' death rate of Listerine® was decreased at 1/8 dilution, and the antibacterial activity of Apple vinegar® was decreased at 1/4 dilution (P <.05). Conclusion. As the number of C. albicans increased, the antibacterial activities of the denture cleansers decrease. In the tablet-type denture cleanser, all denture cleansers showed 100% C. albicans' death rate when used at a dose of 1 tablet. One denture cleanser showed the same antibacterial effect with only 1/3 of a tablet. In the liquid type denture cleanser, the level of dilution required was different for each denture cleanser. [ABSTRACT FROM AUTHOR]

With the expansion of immune-impaired people during second wave of Covid-19 the case of mucormycosis and aspergillosis caused by different fungi such as Rhizopus oryzae, Candida albicans and Aspergillus niger arose in different states. The current study reveals the molecular interaction of ligand and protein to find the novel and natural drug. The molecular docking was carried out by CB-dock tool and the ligand compound n-heptadecanol-1 were docked with different protein of opportunistic fungi. The most significant outcomes were depicted against C. albicans (−4.6 ​kcal/mol) followed by R. oryzae (−3.9 ​kcal/mol) and A. niger (−3.0 ​kcal/mol). n-heptadecanol-1 showed therapeutic potential and eliminates the issue of drug inadequacy that could act as potential anti-fungal agent.