Targeted delivery of amphotericin B-loaded PLGA micelles displaying lipopeptides to drug-resistant Candida-infected skin.

Amphotericin B (AmB) is an antifungal agent administered for the management of serious systemic fungal infections. However, its clinical application is limited because of its water insolubility and side effects. Herein, to apply the minimum dose of AmB that can be used to manage fungal infections, a targeted drug delivery system was designed using lipopeptides and poly(lactide-co-glycolide) (PLGA). Lipopeptides conjugated with PEGylated distearoyl phosphoethanolamine (DSPE) and short peptides via a maleimide-thiol reaction formed nanosized micelles with PLGA and AmB. The antifungal effects of AmB-loaded micelles containing lipopeptides were remarkably enhanced both in vitro and in vivo. Moreover, the intravenous injection of these micelles demonstrated their in vivo targeting capacity of short peptides in a mouse model infected with drug-resistant Candida albicans. Our findings suggest that short antifungal peptides displayed on the surfaces of micelles represent a promising therapeutic candidate for targeting drug-resistant fungal infections.

Felty Syndrome Presented With Candida albicans Lung Abscess Without Arthritis: A Case Report.

Felty syndrome (FS) is a late manifestation of severe active rheumatoid arthritis (RA). A high index of suspicion or FS is needed in patients who present with neutropaenia and splenomegaly with no initial or obvious identifiable cause. We present the case of a 52-year-old who presented with a one-week history of haemoptysis, fever, and night sweats. The patient was hypotensive, tachycardia, and febrile (38 °C). On examination, bilateral crackles and reduced air entry were identified on the right basal and middle zones. The patient was diagnosed with RA two years prior to this presentation and was not on a disease-modifying antirheumatic drug (DMARD). Haematology showed high inflammatory markers and pancytopenia. Chest X-ray showed a right upper lobe abscess. CT-thorax, abdomen, and pelvis confirmed lung abscesses and hepatosplenomegaly. Candida albicans was detected on the broncho-alveolar lavage. He responded well to antifungal medication and corticosteroids with normalisation of the pancytopenia and inflammatory markers and reduction of the spleen size. This case report details the unusual and early presentation of FS in a patient newly diagnosed with RA and who had no active arthritis. We wish to emphasize the importance of a high index of suspicion in patients with RA regardless of the length of their illness.

Successful treatment of Candida albicans-induced fungal cystitis in a dog using caspofungin: a case report.

A 7-year-old castrated male poodle was brought to the referral Animal Medical Center and diagnosed with diabetes and pancreatitis. One month later, the patient presented with cloudy urine, and ultrasonography revealed a large number of spherical substances. The patient was subsequently diagnosed with fungal cystitis with Candida albicans. Initially, 10.00 mg kg-1 itraconazole was prescribed twice daily for six weeks, and the symptoms of prolonged urination improved; however, the fungal balls persisted in the bladder. The six months later, the patient showed recurrent symptoms, such as dysuria and stranguria; therefore, 5.00 mg kg-1 fluconazole was prescribed twice daily; however, it was not effective. Subsequently, 1.00 mg kg-1 caspofungin once daily was administered for three consecutive days. Finally, the fungal balls in the bladder disappeared. The patient was regularly monitored after completion of treatment and, 17 months later, doing well without recurrence. Few reports exist on the use of caspofungin in veterinary medicine. The recommended dose of caspofungin in dogs remains unknown. In the case of azole-resistant Candida, treatment using caspofungin should be considered; although, additional studies on the established dosing and side effects are needed.

Genotypes analysis and antifungal susceptibility of Candida albicans strains isolated from women with vaginal candidiasis in Jordan using PCR targeting 25SrDNA and ALT repeat sequences of the RPS.

Background & Objectives: Genotypic identification of the etiologic agents of vaginal candidiasis (VC) is of significance in epidemiologic studies and in the establishment of adequate treatment protocol. The aim of this study was to determine the antifungal susceptibility and gene diversity of C. albicans isolated from a group of Jordanian women with VC. Methods: A total of 312 isolates of candida species, recovered from women with vaginal candidiasis who attended gynecology clinics affiliated to three major private hospitals in Amman over a period of five months (July 2020 to December 2020) were included in this study. The isolated Candida were characterized by phenotypic and genotypic means. Genotypic studies were performed using specific PCR primers of the rDNA and RPS genes. Susceptibility testing of all C. albicans isolates was conducted following the National Committee for Clinical Laboratory Standards and E-test strips. Results: Candida albicans was the most dominant Candida spp. that caused VC among the studied population. C. albicans isolates were found to be of three different subtypes at the 25S rDNA gene. All isolates belonged to genotypes A, B and C while genotypes D and E were not detected. The diversity of C. albicans was higher on the basis of RPS region where the use of two markers (P-I and P-II) resulted in the identification of nine distinct C. albicans subtypes. The sensitivity testing revealed variations in the susceptibility of various genotypes to different antifungal drugs. Genotype A isolates were more susceptible to fluconazole, flucytosine and ketoconazole than genotypes B and C. Conclusion: Candida albicans incriminated as etiologic agents of vaginitis among Jordanian women exhibited relationship between various genotypes and antifungal drugs.

The progress and future of the treatment of Candida albicans infections based on nanotechnology.

Systemic infection with Candida albicans poses a significant risk for people with weakened immune systems and carries a mortality rate of up to 60%. However, current therapeutic options have several limitations, including increasing drug tolerance, notable off-target effects, and severe adverse reactions. Over the past four decades, the progress in developing drugs to treat Candida albicans infections has been sluggish. This comprehensive review addresses the limitations of existing drugs and summarizes the efforts made toward redesigning and innovating existing or novel drugs through nanotechnology. The discussion explores the potential applications of nanomedicine in Candida albicans infections from four perspectives: nano-preparations for anti-biofilm therapy, innovative formulations of "old drugs" targeting the cell membrane and cell wall, reverse drug resistance therapy targeting subcellular organelles, and virulence deprivation therapy leveraging the unique polymorphism of Candida albicans. These therapeutic approaches are promising to address the above challenges and enhance the efficiency of drug development for Candida albicans infections. By harnessing nano-preparation technology to transform existing and preclinical drugs, novel therapeutic targets will be uncovered, providing effective solutions and broader horizons to improve patient survival rates.

A Simple, Fast, and Reliable Method for the Identification of Candida albicans.

Background: Candida is one of the common pathogens in nosocomial infections. Culture is the gold standard for diagnosing candidemia. Candida albicans is identified via the germ tube test, which uses serum as the culture medium, which is costly and time-consuming. This study was conducted to evaluate and compare a relatively simple, fast, and reliable method for the detection of Candida albicans. Methods: We conducted this randomized case study at Taipei City Hospital (TCH) from January 2023 to August 2023, with a total of 30 specimen culture reports collected and confirmed to be cases of Candida albicans infection. A germ tube test was performed in a 37°C water bath using serum, plasma, and safe plasma products (Fresh Frozen Plasma, FFP). Further, the same procedures were repeated with the addition of 22% bovine serum albumin (BSA) to the identification/culture. Results: By adding BSA, more than 50% of the budding phenomenon was observed in 40 minutes, which shortened the diagnosis time compared with the traditional method (2-3 hours). Using BSA can shorten the identification time for early clinical medication and improve the quality of medical care. Conclusion: Using safer plasma products for germ tube test of candidiasis not only reduced the risk of infection for medical technicians but could also replace the serum used in traditional methods to increase convenience and save time. This study proposed BSA as a germ tube induction medium enhancer, which reduced the culture time, thereby enabling quicker diagnosis of C. albicans infections.

Bioadhesive polymer in antifungal drug delivery for therapeutic treatment of candidiasis.

Candida species are the primary cause of candidiasis, a common yeast infection, with Candida albicans being the most prevalent pathogen. These infections often infiltrate the body through cutaneous and vaginal routes. Given the potential severity of some Candida infections, particularly invasive cases, there is a critical need for effective antifungal treatments. Controlled drug delivery strategies have been developed to achieve optimal release kinetics and precise targeting of active agents, especially in fungal infection therapeutics. Consequently, significant attention has been focused on exploring and utilizing bioadhesive polymers to enhance the performance of drug delivery systems for antifungal medications. Bioadhesive drug delivery systems aim to sustain the release of therapeutic agents, reducing the need for frequent dosing. This article provides a comprehensive review of scientific investigations into the use of antifungal drugs within bioadhesive drug delivery systems for treating candidiasis, locally and systemically. The evaluation covers the efficacy of these systems against candidiasis, factors affecting prolonged contact at the application site, and the underlying mechanisms of drug delivery.

Antifungal Activity of Ocimum tenuiflorum and Ocimum gratissimum Herbal Formulation-Based Oral Rinse Against Candida albicans.

Background Candida albicans is a common fungal pathogen responsible for oral infections, posing significant health challenges. Traditional antifungal treatments often come with side effects and resistance issues, highlighting the need for effective natural alternatives. O. tenuiflorum and Ocimum gratissimum are known for their medicinal properties, including antifungal activity. Objective This study aimed to evaluate the antifungal effectiveness of an O. tenuiflorum and O. gratissimum herbal formulation-based oral rinse against C. albicans. Methods Antifungal activity was measured using agar well diffusion, time-kill curve assays, and analyses of cytoplasmic and protein leakage. The herbal rinse was tested at concentrations of 25 µg/mL, 50 µg/mL, and 100 µg/mL, and compared to a commercial oral rinse. Results The herbal rinse demonstrated strong antifungal effects that increased with concentration. At 100 µg/mL, it produced a 13 mm zone of inhibition, outperforming the commercial rinse's 11 mm. The time-kill assay revealed that the 100 µg/mL concentration reduced fungal counts to 103 CFU/mL within 5 hours, on par with the commercial rinse. Cytoplasmic leakage analysis showed an optical density of 0.42 at 100 µg/mL, close to the commercial rinse's 0.45. Protein leakage analysis indicated an optical density of 0.52 at 100 µg/mL, slightly higher than the commercial rinse's 0.51. Conclusion The O. tenuiflorum and O. gratissimum herbal formulation-based oral rinse exhibit potent antifungal activity against C. albicans, rivaling and even surpassing commercial rinses at higher concentrations. This study underscores the potential of this natural oral rinse as a powerful alternative for managing oral fungal infections, meriting further research and clinical trials to confirm its long-term safety and efficacy.

Lactobacillus johnsonii is a dominant Lactobacillus in the murine oral mucosa and has chitinase activity that compromises fungal cell wall integrity.

The oral microbiome is a critical determinant of health and disease, as interactions between oral microorganisms can influence their physiology and the development or severity of oral infections. Lactobacilli have a widely recognized antagonistic relationship with Candida albicans and may exhibit probiotic properties that limit oral fungal infection. We previously reported that Lactobacillus johnsonii strain MT4, an oral strain isolated from C57BL/6 mice, can induce global changes in the murine oral microbiome and has anti-Candida activity in vitro. To build on this information, we analyzed its abundance on the mouse oral mucosa, tested its impact on the severity and progression of oropharyngeal candidiasis (OPC) in a mouse model, and further explored the mechanism of antifungal activity in vitro. Our findings reveal that L. johnsonii MT4 is a dominant cultivable Lactobacillus in the oral mucosa of C57BL/6 mice. Strain MT4 has chitinase activity against C. albicans, which damages the cell wall and compromises fungal metabolic activity. Oral inoculation with strain MT4 causes a reduction in the Candida-induced rise in the abundance of oral enterococci and oral mucosal damage. This research underscores the potential of L. johnsonii strain MT4 as a novel probiotic agent in the prevention or management of OPC, and it contributes to a better understanding of the role of oral bacterial microbiota role in the pathogenesis of fungal infections. IMPORTANCE: The interactions between the opportunistic pathogen Candida albicans and resident oral bacteria are particularly crucial in maintaining oral health. Emerging antifungal drug-resistant strains, slow-paced drug discovery, and the risk of side effects can compromise the effectiveness of current treatments available for oropharyngeal candidiasis. This study advances the search for alternative microbiome-targeted therapies in oral fungal infections. We report that Lactobacillus johnsonii strain MT4 prevents the Candida-induced bloom of dysbiotic oral enterococci and reduces oral mucosal lesions in an oropharyngeal candidiasis murine model. We also show that this strain directly compromises the cell wall and reduces fungal metabolic activity, partly due to its chitinase activity.

Transcriptomics analysis reveals the effect of Pulsatilla Decoction Butanol Extract on endoplasmic reticulum and peroxisome function of Candida albicans in hyphal state.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine formula known as Pulsatilla decoction was utilized to treat conditions such as bacterial dysentery, ulcerative colitis, and fungal infections like vulvovaginal candidiasis (VVC) caused by Candida albicans (C. albicans). In our prior research, it was shown that the n-butanol extract from Pulsatilla Decoction (BEPD) exhibited effective inhibition of C. albicans. Nevertheless, the exact mechanism by which BEPD hinders hyphal growth, a critical virulence factor of C. albicans, remains unclear. AIM OF THE STUDY: In the present study, the inhibitory effect and mechanism of the BEPD on C. albicans hyphal growth was predicted by transcriptome analysis, and further verified by in vitro and in vivo experiments. MATERIALS AND METHODS: The BEPD was prepared and C. albicans was cultured to induce the hyphal state. Transcriptome analysis was conducted to predict the significant difference in enrichment genes and signaling pathways in the inhibitory effect of BEPD on C. albicans hyphae. Various methods, such as spot assay, time-growth curve analysis, Confocal laser scanning microscope (CLSM), scanning electron microscope (SEM), transmission electron microscope (TEM), flow cytometry, and spectrophotometer, were used to assess the effect of BEPD on hyphal structure and growth activity, lipid peroxidation level, peroxidase (CAT) activity, superoxide dismutase (SOD) activity, and apoptosis of C. albicans. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to examine the expression levels of genes associated with endoplasmic reticulum and peroxisome function. The VVC model was employed to evaluate the influence of BEPD on the growth of C. albicans hyphae in vivo. RESULT: The growth of C. albicans hyphae on solid culture media was significantly inhibited by BEPD. CLSM showed that the length of C. albicans hyphae was decreased and their vitality was lowered. SEM indicated that the hyphae of C. albicans were fractured, while TEM revealed damage to the organelles within the cells. GO enrichment and KEGG pathways analysis from transcriptomic data demonstrated that BEPD effectively suppressed the functioning of the endoplasmic reticulum and peroxisomes in C. albicans hyphae. RT-qPCR verified the decreased expression of genes associated with endoplasmic reticulum and peroxisome function by BEPD. Investigation of the endoplasmic reticulum revealed that BEPD elevated levels of reactive oxygen species (ROS) and apoptosis, indicating endoplasmic reticulum stress, as well as malondialdehyde (MDA), a marker of oxidative stress. Additionally, BEPD was shown to lower the activities of catalase (CAT) and superoxide dismutase (SOD). In animal trials, BEPD effectively hindered the growth of C. albicans hyphae in the vaginas of mice with VVC, thus reducing immune inflammatory damage to the vaginal mucosa of these mice. CONCLUSION: This study demonstrates that BEPD has an inhibitory effect on hyphae, which are an important virulence factor of C. albicans. This effect may be related to BEPD's inhibitory effect on endoplasmic reticulum (ER) and peroxisome function. The findings suggest that BEPD could potentially play a therapeutic role in C. albicans infectious diseases by inhibiting hyphae.

Clinical aPDT's effect on Candida albicans: Antifungal susceptibility, virulence gene expression, and correlation with leukocyte and neutrophil counts.

BACKGROUND: Our previous clinical trial demonstrated that antimicrobial photodynamic therapy (aPDT) with methylene blue (MB) and potassium iodide (KI) effectively killed Candida albicans (C. albicans) in adult AIDS patients with oral candidiasis, regardless of biofilm formation or 25S rDNA genotype. This study evaluated changes in antifungal susceptibility and virulence gene expression in C. albicans before and after aPDT, and explored factors related to clinical aPDT efficacy. METHODS: Twenty-one adult AIDS patients with C. albicans oral candidiasis were divided into Group a (400 µM MB, N = 11) and Group b (600 µM MB, N = 10). Both groups received two aPDT treatments, where MB was applied for 5 min, followed by 300 mM KI, and illuminated for 30 min (37.29 J/cm²). C. albicans isolates were collected before and after treatment to assess antifungal susceptibility (fluconazole, itraconazole, flucytosine, amphotericin B) and gene expression (CAT1, HWP1). Peripheral blood tests were analyzed for correlations with aPDT efficacy. RESULTS: aPDT reduced minimum inhibitory concentration (MIC) values for amphotericin B, fluconazole, and flucytosine, with significant reductions primarily after the first treatment. MIC reductions differed between groups, with Group a showing greater decreases in flucytosine and fluconazole MICs, and Group b in amphotericin B MICs. No significant changes in CAT1 or HWP1 expression were observed. Clinical efficacy of aPDT negatively correlated with leukocyte and neutrophil levels. CONCLUSIONS: aPDT effectively reduces MICs of antifungal drugs against C. albicans isolated from treated patients, particularly after the first treatment. The concentration of MB required to reduce MICs varies among different antifungal drugs. aPDT does not alter CAT1 or HWP1 expression, and its clinical efficacy in eradicating C. albicans is negatively associated with leukocyte and neutrophil levels.

Proposing an Affordable Plasma Device for Polymer Surface Modification and Microbial Inactivation.

This study proposes an affordable plasma device that utilizes a parallel-plate dielectric barrier discharge geometry with a metallic mesh electrode, featuring a straightforward 3D-printed design. Powered by a high-voltage supply adapted from a cosmetic plasma device, it operates on atmospheric air, eliminating the need for gas flux. Surface modification of polyethylene treated with this device was characterized and showed that the elemental composition after 15 min of plasma treatment decreased the amount of C to ~80 at% due to the insertion of O (~15 at%). Tested against Candida albicans and Staphylococcus aureus, the device achieved a reduction of over 99% in microbial load with exposure times ranging from 1 to 10 min. Simultaneously, the Vero cell viability remained consistently high, namely between 91% and 96% across exposure times. These results highlight this device's potential for the surface modification of materials and various infection-related applications, boasting affordability and facilitating effective antimicrobial interventions.

SARS-CoV-2 reactivates fungal-associated Hemophagocytic lymphohistiocytosis: Case report and review of the literature.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease characterized by the uncontrolled activation of the immune system, resulting in a high clinical mortality rate. A 56-year-old Chinese female presented at the emergency room with symptoms including fever, fatigue, nausea, vomiting, cough, shortness of breath, and chest tightness. Laboratory investigations demonstrated decreased levels of white blood cells, hemoglobin, and platelets while interleukin-6 and ferritin exhibited significant elevations. She was subsequently admitted to the hematology department, where she was diagnosed with HLH caused by a Candida infection. Following treatment with antifungal agents, glucocorticoids, antiemetics, diuretics, and hepatoprotective therapy, the patient's condition has shown improvement. However, after being infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the patient experienced a reactivation of HLH, resulting in a more severe clinical presentation and complications compared to the initial onset. Although the patient's condition improved after the administration of antiviral drugs, etoposide, glucocorticoids, cyclosporin, and intravenous immunoglobulin, this case highlights the possibility of disease reactivation during the recovery phase of HLH. This should raise the attention of medical professionals.

Vulvovaginal candidiasis, an increasing burden to women in the tropical regions attending Bharatpur Hospital, Chitwan.

Vulvovaginal candidiasis is a yeast infection commonly caused by the overgrowth of Candida species in and around the vulva and vagina. Abnormal vaginal discharge, itching and irritation, swelling and redness of the vaginal area, pain during sexual intercourse, and dyspareunia are important clinical findings of the infection. Currently, the infection is one of the growing burdens to married women. Moreover, the infection with antifungal-resistant Candida species adds challenges to managing the disease. Hence, this study was conducted to identify the different Candida species causing vulvovaginal candidiasis and to determine its susceptibility pattern against different antifungal drugs. A hospital-based cross-sectional and quantitative study was conducted for the period of six months from September 2022 to March 2023 among symptomatic married women in the Gynecology and Obstetrics Department of Bharatpur Hospital, Chitwan. A total of 300 symptomatic cases were enrolled in the study. Candida species were isolated from vaginal swabs following standard microbiological procedures and antifungal susceptibility testing was performed with different antifungal agents. The total prevalence of vulvovaginal candidiasis was found to be 37.3 % (112/300). Among different isolates, Candida albicans was found to be the most predominant (52.6 %), followed by Candida glabrata (29.3 %) among non-albicans. Women from the age group 25-35 years were found to be more infected (47.3 %) and the relationship between contraceptive use and vulvovaginal candidiasis was found to be statistically significant (p < 0.05). Candida species showed higher susceptibility toward Amphotericin-B (68.1 %), followed by fluconazole (Diflucan), and Clotrimazole (50.9 %). Whereas the least susceptibility was observed to Voriconazole (27.6 %) and Itraconazole (35.30 %). Candida albicans was comparatively more susceptible to different antifungal drugs than non-albicans species. Candida parapsilosis was only susceptible to Amphotericin-B and the increasing incidence of vaginal candidiasis due to non-albicans Candida indicates the need for routine speciation of Candida.

Antifungal activities of Equol against Candida albicans in vitro and in vivo.

Candida albicans is an opportunistic fungal pathogen that can cause systemic infections in immunocompromised individuals. Morphological transition and biofilm formation are major virulence factors of C. albicans. Moreover, biofilm enhances resistance to antifungal agents. Therefore, it is urgent to identify new and effective compounds to target the biofilm of C. albicans. In the present study, the antifungal activities of equol against C. albicans were investigated. In vitro, the microdilution analysis and spot assay result showed that equol exhibited potent inhibitory activities against C. albicans. Further investigations confirmed that the antifungal effects of equol involved interference with the transition from yeast to hypha and biofilm formation of C. albicans. In addition, transcriptome sequencing and reverse transcription-quantitative PCR (qRT-PCR) analysis showed that equol significantly downregulated the expression of several genes in the Ras1-cAMP-PKA pathway related to hyphae and biofilm formation and significantly upregulated the expression of the negative transcriptional repressors RFG1 and TUP1. Moreover, equol effectively reduced the production of cAMP, a key messenger in the Ras1-cAMP-PKA pathway, while supplementation with cAMP partly rescued the equol-induced defects in hyphal development. Furthermore, in a mouse model of systemic candidiasis (SC), equol treatment significantly decreased the fungal burden (liver, kidneys, and lung) in mice and local tissue damage, while enhancing the production of interleukin-10 (IL-10). Together, these findings confirm that equol is a potentially effective agent for treatment of SC.

Association between oral lichen planus and Candida albicans infection: a systematic review and meta-analysis.

This study examines the potential association between Oral Lichen Planus (OLP) and Candida albicans infection, exploring its potential impact on the development of OLP. A meta-analysis of individual case-control studies was performed, estimating odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). A quality assessment of the literature was conducted using the Newcastle-Ottawa Scale (NOS). Due to considerable heterogeneity in the selected studies, subgroup analyses were performed based on geographical location and recruitment methods. No significant publication bias was detected. A sensitivity analysis validated the robustness of the findings when applying a random-effects model. The meta-analysis included ten studies, comprising 1,124 OLP patients and 1,063 healthy controls. Results indicated a significantly higher detection rate of Candida albicans in OLP patients compared to healthy controls (OR = 1.74, P = 0.003, 95% CI: 1.20, 2.52). Additionally, an increased risk of Candida albicans infection was observed in erosive OLP (E-OLP) patients compared to healthy controls (OR = 3.97, 95% CI: 2.31, 6.84, P < 0.00001). These findings suggest a complex interplay between OLP and Candida albicans, highlighting the need for further research to elucidate the varying susceptibilities among different clinical types of OLP. This study provides novel insights for future research directions and clinical treatment strategies in this field.

Synergistic in vitro activity and mechanism of KBN lotion and miconazole nitrate against drug-resistant Candida albicans biofilms.

Background: In the face of increasing antifungal resistance among Candida albicans biofilms, this study explores the efficacy of a combined treatment using Kangbainian lotion (KBN) and miconazole nitrate (MN) to address this challenge. Methods: Using UPLC-Q-TOF/MS Analysis for Identification of Active Compounds in KBN Lotion; FICI for synergy evaluation, XTT and ROS assays for biofilm viability and oxidative stress, fluorescence and confocal laser scanning microscopy (CLSM) for structural and viability analysis, and real-time fluorescence for gene expression. Conclusion: Our study indicates that the combined application of KBN and MN somewhat impacts the structural integrity of Candida albicans biofilms and affects the expression of several key genes involved in biofilm formation, including ALS1, ALS3, HWP1, HSP90, and CSH1. These preliminary findings suggest that there may be a synergistic effect between KBN and MN, potentially influencing not only the structural aspects of fungal biofilms but also involving the modulation of genetic pathways during their formation.

Antimicrobial and synergistic effects of lemongrass and geranium essential oils against Streptococcus mutans, Staphylococcus aureus, and Candida spp.

BACKGROUND: The oral cavity harbors more than 700 species of bacteria, which play crucial roles in the development of various oral diseases including caries, endodontic infection, periodontal infection, and diverse oral diseases. AIM: To investigate the antimicrobial action of Cymbopogon Schoenanthus and Pelargonium graveolens essential oils against Streptococcus mutans, Staphylococcus aureus, Candida albicans, Ca. dubliniensis, and Ca. krusei. METHODS: Minimum microbicidal concentration was determined following Clinical and Laboratory Standards Institute documents. The synergistic antimicrobial activity was evaluated using the Broth microdilution checkerboard method, and the antibiofilm activity was evaluated with the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. Data were analyzed by one-way analysis of variance followed by the Tukey post-hoc test (P ≤ 0.05). RESULTS: C. schoenanthus and P. graveolens essential oils were as effective as 0.12% chlorhexidine against S. mutans and St. aureus monotypic biofilms after 24 h. After 24 h P. graveolens essential oil at 0.25% was more effective than the nystatin group, and C. schoenanthus essential oil at 0.25% was as effective as the nystatin group. CONCLUSION: C. schoenanthus and P. graveolens essential oils are effective against S. mutans, St. aureus, Ca. albicans, Ca. dubliniensis, and Ca. krusei at different concentrations after 5 min and 24 h.

Nanoscale fluconazole-constructed metal-organic frameworks with smart drug release for eradication of Candida biofilms in vulvovaginitis infection.

Fungal infections associated with oral, gynecological, and skin ailments pose significant clinical challenges. The presence of biofilms often hampers the efficacy of conventional antifungal drugs owing to the complex microenvironment they create. In this study, the widely used antifungal medication fluconazole is utilized as a foundational component to be incorporated into zinc 2-methylimidazolate frameworks, resulting in the synthesis of nanoscale fluconazole-constructed metal-organic frameworks (F-ZIF). The F-ZIF is constructed through coordination interactions between zinc and fluconazole, retaining the structure and pH-responsiveness of the zinc 2-methylimidazolate framework. The pH-responsiveness F-ZIF makes sure the fluconazole can be released in acidic biofilm, which prevents the undesired release in healthy tissue, resulting in good biocompatibility both in vitro and in vivo. The in vitro studies demonstrated that F-ZIF exhibits enhanced efficacy in eradicating fungal pathogens in their biofilm growth state compared with the free fluconazole. Furthermore, in vivo experiments reveal the better effectiveness of F-ZIF in treating Candida albicans-induced vulvovaginal candidiasis, and less infection-related inflammation was observed. Hence, the one-port synthetic F-ZIF presents a promising solution for addressing fungal biofilm-related infections.

Mining for antifungal agents to inhibit biofilm formation of Candida albicans: A study on green synthesis, antibiofilm, cytotoxicity, and in silico ADME analysis of 2-amino-4H-pyran-3-carbonitrile derivatives.

Candida albicans (C. albicans) biofilm infections are quite difficult to manage due to their resistance against conventional antifungal drugs. To address this issue, there is a desperate need for new therapeutic drugs. In the present study, a green and efficient protocol has been developed for the synthesis of 2-amino-4H-pyran-3-carbonitrile scaffolds 4a-i, 6a-j, and 8a-g by Knoevenagel-Michael-cyclocondensation reaction between aldehydes, malononitrile, and diverse enolizable C-H activated acidic compounds using guanidinium carbonate as a catalyst either under grinding conditions or by stirring at room temperature. This protocol is operationally simple, rapid, inexpensive, has easy workup and column-free purification. A further investigation of the synthesized compounds was conducted to examine their antifungal potential and their ability to inhibit the growth and development of biofilm-forming yeasts like fungus C. albicans. According to our findings, 4b, 4d, 4e, 6e, 6f, 6g, 6i, 8c, 8d, and 8g were found to be active and potential inhibitors for biofilm infection causing C. albicans. The inhibition of biofilm by active compounds were observed using field emission scanning electron microscopy (FESEM). Biofilm inhibiting compounds were also tested for in vitro toxicity by using 3T3-L1 cell line, and 4b, 6e, 6f, 6g, 6i, 8c, and 8d were found to be biocompatible. Furthermore, the in silico ADME descriptors revealed drug-like properties with no violation of Lipinski's rule of five. Hence, the result suggested that synthesized derivatives could serve as a useful aid in the development of novel antifungal compounds for the treatment of fungal infections and virulence in C. albicans.