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Candida albicans (C. albicans), a common fungal pathogen, poses a significant threat to immunocompromised individuals, particularly due to the emergence of resistance against echinocandins, a primary class of antifungal agents. Yck2 protein, a key regulator of cell wall integrity and signaling pathways in C. albicans, was targeted to overcome this resistance. A virtual screening was used to identify Yck2 inhibitors from marine bacterial compounds. Further re-docking, molecular dynamics simulations, and various analyses such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bonding, free binding energy calculations, and RG-RMSD-based free energy landscape were conducted to evaluate the efficacy and stability of the identified compounds. Among the compounds screened, CMNPD27166 and CMNPD27283 emerged as the most promising candidates, demonstrating superior binding affinities, enhanced stability, and favorable interaction dynamics with Yck2, surpassing both the control and other compounds in efficacy. In contrast, CMNPD19660 and CMNPD24402, while effective, showed lesser potential. These findings highlight the utility of computational drug discovery techniques in identifying and optimizing potential therapeutic agents and suggest that marine-derived molecules could significantly impact the development of novel antifungal therapies. Further experimental validation of the leading candidates, CMNPD27166 and CMNPD27283, is recommended to confirm their potential as effective antifungal agents against echinocandin-resistant C. albicans infections. [ABSTRACT FROM AUTHOR]

Background: Candida africana is an emergent variant that has been listed as a new species or variety within the Candida albicans complex since 2001. It has a worldwide intra-albicans complex pooled prevalence of 1.67% and varies between 0 and 8% depending on geographical region. We present the results of a pilot study on its prevalence in Uganda. Methodology: We conducted a cross-sectional study between March and June 2023. We recruited 4 pregnant women from Mulago Specialized Women and Neonatal Hospital, 102 from Kawempe National Referral Hospital, and 48 from Sebbi Hospital. Vaginal swabs were tested using microscopy, culture and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF). Results: The prevalence of C. africana was zero. Out of the 103 isolates, the majority (81.553%) were identified as Candida albicans, followed by Nakeseomyces glabrata (13.592%) and Pichia kudriavzevii (1.942%). Cyberlindnera jadinii, Candida tropicalis, and Candida parapsilosis each accounted for 0.971% of the isolates. Conclusion: The prevalence of C. africana in Uganda is zero. However, large-scale cross-sectional studies, including studies involving the collection of vaginal samples from both urban and rural settings in Uganda and the use of both MALDI-TOF- and PCR-based laboratory methods, are needed to fully describe the public health burden of C. africana infections. [ABSTRACT FROM AUTHOR]

Background: Organellar transcriptomes are relatively under-studied systems, with data related to full-length transcripts and posttranscriptional modifications remaining sparse. Direct RNA sequencing presents the possibility of accessing a previously unavailable layer of information pertaining to transcriptomic data, as well as circumventing the biases introduced by second-generation RNA-seq platforms. Direct long-read ONT sequencing allows for the isoform analysis of full-length transcripts and the detection of posttranscriptional modifications. However, there are still relatively few projects employing this method specifically for studying organellar transcriptomes. Results: Candida albicans is a promising model for investigating nucleo-mitochondrial interactions. This work comprises ONT sequencing of the Candida albicans mitochondrial transcriptome along with the development of a dedicated data analysis pipeline. This approach allowed for the detection of complete transcript isoforms and posttranslational RNA modifications, as well as an analysis of C. albicans deletion mutants in genes coding for the 5' and 3' mitochondrial RNA exonucleases CaPET127 and CaDSS1. It also enabled for corrections to previous studies in terms of 3' and 5' transcript ends. A number of intermediate splicing isoforms was also discovered, along with mature and unspliced transcripts and changes in their abundances resulting from disruption of both 5' and 3' exonucleolytic processing. Multiple putative posttranscriptional modification sites have also been detected. Conclusions: This preliminary work demonstrates the suitability of direct RNA sequencing for studying yeast mitochondrial transcriptomes in general and provides new insights into the workings of the C. albicans mitochondrial transcriptome in particular. It also provides a general roadmap for analyzing mitochondrial transcriptomic data from other organisms. [ABSTRACT FROM AUTHOR]

Candida albicans has been listed in the critical priority group by the WHO in 2022 depending upon its contribution in invasive candidiasis and increased resistance to conventional drugs. Drug repurposing offers an efficient, rapid, and cost-effective solution to develop alternative therapeutics against pathogenic microbes. Alexidine dihydrochloride (AXD) and hexachlorophene (HCP) are FDA approved anti-cancer and anti-septic drugs, respectively. In this study, we have shown antifungal properties of AXD and HCP against the wild type (reference strain) and clinical isolates of C. albicans. The minimum inhibitory concentrations (MIC50) of AXD and HCP against C. albicans ranged between 0.34 and 0.69 µM and 19.66–24.58 µM, respectively. The biofilm inhibitory and eradication concentration of AXD was reported comparatively lower than that of HCP for the strains used in the study. Further investigations were performed to understand the antifungal mode of action of AXD and HCP by studying virulence features like cell surface hydrophobicity, adhesion, and yeast to hyphae transition, were also reduced upon exposure to both the drugs. Ergosterol content in cell membrane of the wild type strain was upregulated on exposure to AXD and HCP both. Biochemical analyses of the exposed biofilm indicated reduced contents of carbohydrate, protein, and e-DNA in the extracellular matrix of the biofilm when compared to the untreated control biofilm. AXD exposure downregulated activity of tissue invading enzyme, phospholipase in the reference strain. In wild type strain, ROS level, and activities of antioxidant enzymes were found elevated upon exposure to both drugs. FESEM analysis of the drug treated biofilms revealed degraded biofilm. This study has indicated mode of action of antifungal potential of alexidine dihydrochloride and hexachlorophene in C. albicans. [ABSTRACT FROM AUTHOR]

This study provides valuable insights into the structural and chemical characteristics of zinc oxide nanoparticles (ZnO NPs), enhancing their antimicrobial efficacy against Gram-positive bacteria and fungi. Structural and optical analyses of ZnO NPs synthesized via a green route revealed a floral morphology at 450 °C with petal sizes averaging ~ 20.56 nm. Size and strain characteristics were extensively investigated using mathematical techniques such as the Scherrer and Williamson–Hall methods. The influence of key parameters, including nanoparticle concentration and UV exposure, on the antimicrobial efficacy of UV-irradiated ZnO nanoparticles was examined. Biochemical assays suggest that the synthesized ZnO nanoparticles hold potential as novel antimicrobial agents for effectively controlling microbial infections. Notably, oxidative stress markers showed a significant increase in protein carbonyl formation in Staphylococcus aureus (31,237 nmol/mg) and Candida albicans (29,109 nmol/mg). Additionally, the time-dependent antimicrobial effect revealed reduction in microbial growth over specified periods, indicating prolonged antimicrobial activity. The molecular-level study demonstrates that the antimicrobial activity of ZnO NPs, particularly upon UV activation, is mediated through the production of ROS, leading to oxidative stress, protein damage, enzymatic activity disruption, and membrane integrity compromise, ultimately resulting in microbial cell death. [ABSTRACT FROM AUTHOR]

Background: Genital tract is the portal of entry for numerous sexually and non-sexually transmitted diseases. A number of bacterial and non-bacterial infections exist that affect the female reproductive tract and cause vaginal discharge. Candida species are among important opportunistic pathogens causing candidiasis in human worldwide. These yeast species are of public health concern nowadays. Aim: This study aimed at comparing the prevalence of candidiasis among single and married women attending Rwanda Military Hospital. The study population comprises of single and married women. Methodology: This was a retrospective study where data was collected from Rwanda Military Hospital. Results: The results of this study showed that the incidence of candidiasis was higher in married women when compared with single women. The prevalence of candidiasis in married women was 128(74.4%), while in single women is 44(25.6%). It was observed in this study that the distribution of candidiasis among married and single is statistically significant (p<0.05). Results also show that out of 172 single and married women, more cases of candidiasis were observed within the age range of 21-30 years, 66 (44.2%) were infected with candida albicans, 31-40 years had a prevalence of 55(32%) and 11-20 years had a prevalence of 13(7.6%). The overall of cases of candida other than C. albicans observed was 15.1%. Conclusion: This study showed that married and single women are predisposed to candidiasis. It is therefore important to give opportunistic pathogens like Candida species attention in women especially among married ones as they are mostly affected by this candidiasis. [ABSTRACT FROM AUTHOR]

Abstract Background Candida africana is an emergent variant that has been listed as a new species or variety within the Candida albicans complex since 2001. It has a worldwide intra-albicans complex pooled prevalence of 1.67% and varies between 0 and 8% depending on geographical region. We present the results of a pilot study on its prevalence in Uganda. Methodology We conducted a cross-sectional study between March and June 2023. We recruited 4 pregnant women from Mulago Specialized Women and Neonatal Hospital, 102 from Kawempe National Referral Hospital, and 48 from Sebbi Hospital. Vaginal swabs were tested using microscopy, culture and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF). Results The prevalence of C. africana was zero. Out of the 103 isolates, the majority (81.553%) were identified as Candida albicans, followed by Nakeseomyces glabrata (13.592%) and Pichia kudriavzevii (1.942%). Cyberlindnera jadinii, Candida tropicalis, and Candida parapsilosis each accounted for 0.971% of the isolates. Conclusion The prevalence of C. africana in Uganda is zero. However, large-scale cross-sectional studies, including studies involving the collection of vaginal samples from both urban and rural settings in Uganda and the use of both MALDI-TOF- and PCR-based laboratory methods, are needed to fully describe the public health burden of C. africana infections.

Abstract Background Organellar transcriptomes are relatively under-studied systems, with data related to full-length transcripts and posttranscriptional modifications remaining sparse. Direct RNA sequencing presents the possibility of accessing a previously unavailable layer of information pertaining to transcriptomic data, as well as circumventing the biases introduced by second-generation RNA-seq platforms. Direct long-read ONT sequencing allows for the isoform analysis of full-length transcripts and the detection of posttranscriptional modifications. However, there are still relatively few projects employing this method specifically for studying organellar transcriptomes. Results Candida albicans is a promising model for investigating nucleo-mitochondrial interactions. This work comprises ONT sequencing of the Candida albicans mitochondrial transcriptome along with the development of a dedicated data analysis pipeline. This approach allowed for the detection of complete transcript isoforms and posttranslational RNA modifications, as well as an analysis of C. albicans deletion mutants in genes coding for the 5' and 3' mitochondrial RNA exonucleases CaPET127 and CaDSS1. It also enabled for corrections to previous studies in terms of 3’ and 5’ transcript ends. A number of intermediate splicing isoforms was also discovered, along with mature and unspliced transcripts and changes in their abundances resulting from disruption of both 5’ and 3’ exonucleolytic processing. Multiple putative posttranscriptional modification sites have also been detected. Conclusions This preliminary work demonstrates the suitability of direct RNA sequencing for studying yeast mitochondrial transcriptomes in general and provides new insights into the workings of the C. albicans mitochondrial transcriptome in particular. It also provides a general roadmap for analyzing mitochondrial transcriptomic data from other organisms.

Abstract Invasive candidiasis (IC) is a notable healthcare-associated fungal infection, characterized by high morbidity, mortality, and substantial treatment costs. Candida albicans emerges as a principal pathogen in this context. Recent academic advancements have shed light on the critical role of exosomes in key biological processes, such as immune responses and antigen presentation. This burgeoning body of research underscores the potential of exosomes in the realm of medical diagnostics and therapeutics, particularly in relation to fungal infections like IC. The exploration of exosomal functions in the pathophysiology of IC not only enhances our understanding of the disease but also opens new avenues for innovative therapeutic interventions. In this investigation, we focus on exosomes (Exos) secreted by macrophages, both uninfected and those infected with C. albicans. Our objective is to extract and analyze these exosomes, delving into the nuances of their protein compositions and subgroups. To achieve this, we employ an innovative technique known as Proximity Barcoding Assay (PBA). This methodology is pivotal in our quest to identify novel biological targets, which could significantly enhance the diagnostic and therapeutic approaches for C. albicans infection. The comparative analysis of exosomal contents from these two distinct cellular states promises to yield insightful data, potentially leading to breakthroughs in understanding and treating this invasive fungal infection. In our study, we analyzed differentially expressed proteins in exosomes from macrophages and C. albicans -infected macrophages, focusing on proteins such as ACE2, CD36, CAV1, LAMP2, CD27, and MPO. We also examined exosome subpopulations, finding a dominant expression of MPO in the most prevalent subgroup, and a distinct expression of CD36 in cluster14. These findings are crucial for understanding the host response to C. albicans and may inform targeted diagnostic and therapeutic approaches. Our study leads us to infer that MPO and CD36 proteins may play roles in the immune escape mechanisms of C. albicans. Additionally, the CD36 exosome subpopulations, identified through our analysis, could serve as potential biomarkers and therapeutic targets for C. albicans infection. This insight opens new avenues for understanding the infection's pathology and developing targeted treatments.

Abstract Background Tissue conditioners are used for treating and improving the tissues supporting complete dentures. On the other hand, recent advances in nanotechnology have revolutionized various fields of science, including dentistry. The present study aimed to investigate novel antimicrobial applications of copper oxide nanoparticle-based tissue conditioner used in complete prostheses. Methods The present experimental study included 126 tissue conditioner samples with different concentrations of copper oxide nanoparticles (20%, 10%, 5%, 2.5%, 1.25%, 0.625%, and 0% w/w). The samples were incubated with Enterococcus faecalis, Pseudomonas aeruginosa, and Candida albicans in 24-well plates for 24 h. Then, samples from the wells were re-incubated for 24 h, and the microorganisms were counted. Results The culture media containing E. faecalis and P. aeruginosa showed significantly different growth between different nanoparticle concentrations following 24 h (P

Aim. Evaluation and correction of local antimicrobial protection factors in women with type 2 diabetes mellitus (DM 2) and chronic recurrent vulvovaginal candidiasis (rVVC). Materials and methods. The study involved 100 women undergoing outpatient follow-up at the age of 40.9±5.8 years, with a body mass index of 29.8±3.5. The period was 2022–2023. The examination included anamnesis, collection of anthropometric data, calculation of body weight, microscopic examination of smears from the cervical canal and vagina, Gram-stained before treatment, in the 1st and 3rd months after its completion, identification pathogenic microorganisms using PCR, colposcopy, ultrasound of the pelvic organs. Indicators of glycosylated hemoglobin in the subjects at the control points of the study: at 1 month the average values were 5.9±2.9%, at 3 months – 5.9±3.0%, the average value was 5.9±3.1%. Candida species were identified by the bacteriological method using Sabouraud dextrose agar (growth of colonies of fungi of the genus Candida in an amount of more than 103 CFU/ml). Immunological methods for studying antimicrobial protection factors included studying the number of neutrophil granulocytes (NG) on the surface of the mucous membranes of the vulva and vagina, their phagocytic and NBT-reducing activity in a latex test. Randomization of patients into groups: group 1 included 50 (50%) women with DM 2 who, as part of complex therapy for rVVC received the drug Genferon® 1 intravaginal suppository of 500 thousand units 2 times a day for 10 days and fluconazole 150 mg orally three times with an interval of 72 hours at the first stage of treatment; group 2 included 50 (50%) women who received therapy with fluconazole 150 mg three times with an interval of 72 hours. The maintenance anti-relapse course therapy in both groups included the use of fluconazole 150 mg once a week for 6 months. In group 1st anti-relapse therapy was supplemented by the administration of the drug Genferon® 1 intravaginal suppository of 500 thousand units at night 3 times a week for 3 months, after which the vaginal microbiota was corrected for 2 weeks using vaginal suppositories, containing Lactobacillus acidophilus in an amount of at least 108 CFU. In group 2nd, basic anti-relapse antimycotic therapy was not accompanied by the prescription of any immunomodulatory or probiotic drugs. Results. The etiological agents of rVVC in women of late reproductive age in 79% (n=79) и 28% (n=28), respectively, were C. albicans and C. glabrata, which during the period of acute of the disease were detected by culture in the vaginal discharge at more than 104 CFU/ml. Chronic recurrent course of vulvovaginal candidiasis in women with DM 2 was characterized by exacerbations 4 or more times a year, accompanied by the corresponding clinical picture: white or yellowish-white cheesy discharge from the genital tract, itching or burning in the anogenital area, discomfort in the external genital area, dyspareunia, dysuria, decreased phagocytic activity of NG in vaginal secretions by 25.8%, impairment of their spontaneous and latex-induced NBT-reducing activity by 35.2%, functional reserve by 23.0% relative to reference values. The use of the drug Genferon® as part of complex therapy for rVVC contributed to a decrease in the number of Candida spp. in 1st and 3d months of observation after completion of anti-relapse therapy, normalization of cellular factors of innate immunity of the mucous membranes, faster resolution of the clinical manifestations of an episode of the disease. The decrease in the number of relapses over a 12-month observation period compared to the control group was also facilitated by an increase in the protective properties of the vaginal mucosa due to the restoration of the vaginal microbiota with the help of lactobacilli acidophilus. Conclusion. The etiological agents of rVVC in women of late reproductive age are C. albicans and C. glabrata. Subcompensated DM 2 is a risk factor for rVVC, which requires additional monitoring of microbiological parameters of the vaginal microbiota. rVVC in women with DM 2 is associated with an increase in the number of NG in the vaginal secretion, a decrease in their phagocytic activity and functional reserve compared to the reference values. Combination therapy of rVVC with topical recombinant interferon α2b, benzocaine and taurine in the formulation of Genferon® (suppositories) is an effective method to improve the clinical and immunological efficacy of therapy.

The rise in drug-resistant fungal infections poses a significant public health concern, necessitating the development of new antifungal therapies. We aimed to address this challenge by targeting a yeast casein kinase of Candida albicans for antifungal drug development. The compound library contained 589 chemical structures similar to the previously identified kinase inhibitor GW461484A. Through virtual screening, four compounds with the PubChem IDs 102583821, 12982634, 102487860, and 86260205 were selected based on their binding energies. Hydrophobic bonds and van der Waals interactions stabilised the docked complexes. Comprehensive interaction studies and a 200-nanosecond molecular dynamics simulation suggested that these molecules can maintain stable interactions with the target, as evidenced by satisfactory RMSD and RMSF values. The Rg-RMSD-based Free Energy Landscape of these complexes indicated thermodynamic stability due to the presence of conformers with global minima. These promising findings highlight the potential for developing novel antifungal therapies targeting Yck2 in C. albicans. Further experimental validation is required to assess the efficacy of these compounds as antifungal agents. This research provides a significant step towards combating antifungal resistance and opens up a new avenue for drug discovery. [ABSTRACT FROM AUTHOR]

The control of Candida albicans biofilm formation on dentures made of poly(methyl methacrylate) (PMMA) is an important challenge due to the high resistance to antifungal drugs. Interestingly, the natural compounds undecylenic acid (UDA) and farnesol (FAR) both prevent C. albicans biofilm formation and could have a synergetic effect. We therefore modified PMMA with a combination of UDA and FAR (UDA+FAR), aiming to obtain the antifungal PMMA_UDA+FAR composites. Equal concentrations of FAR and UDA were added to PMMA to reach 3%, 6%, and 9% in total of both compounds in composites. The physico-chemical properties of the composites were characterized by Fourier-transform infrared spectroscopy and water contact angle measurement. The antifungal activity of the composites was tested on both biofilm and planktonic cells with an XTT test 0 and 6 days after the composites' preparation. The effect of the UDA+FAR combination on C. albicans filamentation was studied in agar containing 0.0125% and 0.4% UDA+FAR after 24 h and 48 h of incubation. The results showed the presence of UDA and FAR on the composite and decreases in the water contact angle and metabolic activity of both the biofilm and planktonic cells at both time points at non-toxic UDA+FAR concentrations. Thus, the modification of PMMA with a combination of UDA+FAR reduces C. albicans biofilm formation on dentures and could be a promising anti-Candida strategy. [ABSTRACT FROM AUTHOR]

Introduction: Candida albicans and Streptococcus mutans co-exist in biofilms in the oral cavity. In this study, the impact of S. mutans on the growth of C. albicans within a mixed-species biofilm was examined. Materials and Methods: Single species C. albicans biofilms and mixed species biofilms containing C. albicans and S. mutans at 1:3 and 1:10 ratios were constructed in 6-well microtiter plates. After 24 hours of incubation, the density of resuspended biofilm cells was determined as CFU/ml and used to compare the growth of C. albicans in single species and mixed species biofilms. Results: The CFU/ml of C. albicans in mixed-species biofilms was found to be higher than that in single-species biofilms. Conclusion: S. mutans promotes the growth of C. albicans in a co-inhabited biofilm. [ABSTRACT FROM AUTHOR]

Objectives: Guided bone regeneration (GBR) is a core procedure used to regenerate bone defects. The aim of the study was to investigate the adherence of Candida albicans on six commercially available polytetrafluoroethylene (PTFE) membranes used in GBR procedures and the subsequent clinical consequences. Materials and Methods: Six commercially available PTFE membranes were tested. Two of the membranes had a textured surface and the other four a plane, nontextured one. C. albicans (ATCC 24433) was cultured for 24 h, and its cell surface hydrophobicity was assessed using a modified method. C. albicans adhesion to membrane discs was studied by scanning electron microscopy (SEM) and real‐time polymerase chain reaction (PCR). Results: C. albicans was found to be hydrophobic (77.25%). SEM analysis showed that C. albicans adherence to all membranes examined was characterized by patchy, scattered, and small clustered patterns except for one nontextured membrane with a most rough surface in which a thick biofilm was observed. Real‐time PCR quantification revealed significantly greater adhesion of C. albicans cells to PTFE membranes than the control membrane (p ≤.001) with the membranes having a textured surface exhibiting the highest count of 2680 × 104 cells/ml compared to the count of 707 × 104 cells/mL on those with a nontextured one (p ≤.001). One membrane with nontextured surface, but with most rough surface was found to exhibit the highest count of 3010 × 104 cells/ml (p ≤.05). Conclusion: The results of this study indicate that C. albicans adhesion on membranes' surfaces depends on the degree of surface roughness and/or on the presence of a texture. Textured PTFE membranes and/or membranes high roughness showed significantly more adhered C. albicans cells. These findings can impact the surgeon's choice of GBR membrane and postoperative maintenance. [ABSTRACT FROM AUTHOR]

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 99mTc. 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 68Ga ([68Ga]Ga‐NOTA‐K‐EcgDf1(10)). The [68Ga]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 [68Ga]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. [ABSTRACT FROM AUTHOR]

Background: Tissue conditioners are used for treating and improving the tissues supporting complete dentures. On the other hand, recent advances in nanotechnology have revolutionized various fields of science, including dentistry. The present study aimed to investigate novel antimicrobial applications of copper oxide nanoparticle-based tissue conditioner used in complete prostheses. Methods: The present experimental study included 126 tissue conditioner samples with different concentrations of copper oxide nanoparticles (20%, 10%, 5%, 2.5%, 1.25%, 0.625%, and 0% w/w). The samples were incubated with Enterococcus faecalis, Pseudomonas aeruginosa, and Candida albicans in 24-well plates for 24 h. Then, samples from the wells were re-incubated for 24 h, and the microorganisms were counted. Results: The culture media containing E. faecalis and P. aeruginosa showed significantly different growth between different nanoparticle concentrations following 24 h (P < 0.001), showing a reduction in bacterial growth with increased nanoparticle concentration. Both bacteria did not show any growth at the 20% concentration. However, C. albicans showed significant differences in growth between different nanoparticle concentrations following 48 h (P < 0.001), showing a reduction in growth with increased nanoparticle concentration. Also, the least growth was observed at the 20% concentration. Conclusions: In conclusion, the CuO nanoparticles were prepared using a green synthesis methon in the suitable sizes. Moreover, the tissue conditioners containing CuO nanoparticles showed acceptable antimicrobial properties against E. faecalis, P. aeruginosa, and C. albicans. [ABSTRACT FROM AUTHOR]

The development of new drugs derived from plant sources is of significant interest in modern pharmacy. One of the promising plant sources for introduction into pharmaceuticals is Tripleurospermum inodorum (L.) Sch. Bip., also known as Tripleurospermum perforatum (Merat.) M. This plant has been shown to possess various biological activities, including anti-inflammatory, antimicrobial, and antimycotic activities, among others. However, a review of the current literature reveals a paucity of studies investigating the chemical composition of the herb Tripleurospermum inodorum (L.) Sch. Bip. This study presents the development of a method for obtaining an extract of the herb Tripleurospermum inodorum (L.) Sch. Bip. enriched with flavonoids, harvested before flowering and butonization. This study focused on determining the optimal conditions for extraction, including the concentration of the extractant (ethanol), extraction time, raw material/extractant ratio, extraction frequency, complexation reaction time, amount of aluminum chloride solution, and amount of diluted acetic acid. The results indicate that herbs harvested during this specific period exhibited a higher flavonoid content compared to those collected during butonization and flowering. Moreover, this study demonstrated that the flavonoid content could exceed 7% mg REq/100 g D.W. through a one-hour extraction process. Furthermore, the flavonoid content was found to be 7.65 ± 0.03 mg REq/100 g D.W. following a three-minute ultrasound-assisted extraction process, followed by thermal extraction. A qualitative analysis identified a variety of phenolic compounds in the extract, such as chlorogenic acid, 5-O-p-coumaroylquinic acid, 1-O-p-coumaroylquinic acid, luteolin-7-glucoside, quercetin-3-glucoside, luteolin-7-rutinoside, 3,5-O-dicaffeoylquinic acid, quercetin-3-O-malonylglucoside, apigenin-7-glucoside, luteolin-3-malonylglucoside, cynarin, rhamnetin-3-(O-dimethyl rhamnosyl glucosylglucoside), and luteolin. Moreover, this study demonstrated the antimicrobial, anti-inflammatory, anticoagulant, anti-aggregation, and antioxidant activities of the aqueous alcoholic extract from T. inodorum herb (ETIH) against pathogens such as Staphylococcus aureus, Escherichia coli, and Candida albicans. Additionally, the extract exhibited comparable anti-inflammatory effects on diclofenac sodium. These findings contribute to the understanding of the potential pharmacological applications of the developed herb extract. [ABSTRACT FROM AUTHOR]

Candida albicans (C. albicans), a microbe commonly isolated from Candida vaginitis patients with vaginal tract infections, transforms from yeast to hyphae and produces many toxins, adhesins, and invasins, as well as C. albicans biofilms resistant to antifungal antibiotic treatment. Effective agents against this pathogen are urgently needed. Antimicrobial peptides (AMPs) have been used to cure inflammation and infectious diseases. In this study, we isolated whole housefly larvae insect SVWC peptide 1 (WHIS1), a novel insect single vonWillebrand factor C-domain protein (SVWC) peptide from whole housefly larvae. The expression pattern of WHIS1 showed a response to the stimulation of C. albicans. In contrast to other SVWC members, which function as antiviral peptides, interferon (IFN) analogs or pathogen recognition receptors (PRRs), which are the prokaryotically expressed MdWHIS1 protein, inhibit the growth of C. albicans. Eukaryotic heterologous expression of WHIS1 inhibited C. albicans invasion into A549 and HeLa cells. The heterologous expression of WHIS1 clearly inhibited hyphal formation both extracellularly and intracellularly. Furthermore, themechanismof WHIS1 has demonstrated that it downregulates all key hyphal formation factors (ALS1, ALS3, ALS5, ECE1, HWP1, HGC1, EFG1, and ZAP1) both extracellularly and intracellularly. These data showed that heterologously expressed WHIS1 inhibits C. albicans invasion into epithelial cells by affecting hyphal formation and adhesion factor-related gene expression. These findings provide new potential drug candidates for treating C. albicans infection. [ABSTRACT FROM AUTHOR]

Background: Genital tract is the portal of entry for numerous sexually and non-sexually transmitted diseases. A number of bacterial and non-bacterial infections exist that affect the female reproductive tract and cause vaginal discharge. Candida species are among important opportunistic pathogens causing candidiasis in human worldwide. These yeast species are of public health concern nowadays. Aim: This study aimed at comparing the prevalence of candidiasis among single and married women attending Rwanda Military Hospital. The study population comprises of single and married women. Methodology: This was a retrospective study where data was collected from Rwanda Military Hospital. Results: The results of this study showed that the incidence of candidiasis was higher in married women when compared with single women. The prevalence of candidiasis in married women was 128(74.4%), while in single women is 44(25.6%). It was observed in this study that the distribution of candidiasis among married and single is statistically significant (p<0.05). Results also show that out of 172 single and married women, more cases of candidiasis were observed within the age range of 21-30 years, 66 (44.2%) were infected with candida albicans, 31-40 years had a prevalence of 55(32%) and 11-20 years had a prevalence of 13(7.6%). The overall of cases of candida other than C. albicans observed was 15.1%. Conclusion: This study showed that married and single women are predisposed to candidiasis. It is therefore important to give opportunistic pathogens like Candida species attention in women especially among married ones as they are mostly affected by this candidiasis. [ABSTRACT FROM AUTHOR]

Candida albicans (C. albicans), a common fungal pathogen, poses a significant threat to immunocompromised individuals, particularly due to the emergence of resistance against echinocandins, a primary class of antifungal agents. Yck2 protein, a key regulator of cell wall integrity and signaling pathways in C. albicans, was targeted to overcome this resistance. A virtual screening was used to identify Yck2 inhibitors from marine bacterial compounds. Further re-docking, molecular dynamics simulations, and various analyses such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bonding, free binding energy calculations, and RG-RMSD-based free energy landscape were conducted to evaluate the efficacy and stability of the identified compounds. Among the compounds screened, CMNPD27166 and CMNPD27283 emerged as the most promising candidates, demonstrating superior binding affinities, enhanced stability, and favorable interaction dynamics with Yck2, surpassing both the control and other compounds in efficacy. In contrast, CMNPD19660 and CMNPD24402, while effective, showed lesser potential. These findings highlight the utility of computational drug discovery techniques in identifying and optimizing potential therapeutic agents and suggest that marine-derived molecules could significantly impact the development of novel antifungal therapies. Further experimental validation of the leading candidates, CMNPD27166 and CMNPD27283, is recommended to confirm their potential as effective antifungal agents against echinocandin-resistant C. albicans infections.

Abstract Background In this study, the antimicrobial activity of three different cleanser tablets on S. mutans and C. albicans adhesion to PMMA, polyamide and 3D printed resin was investigated. Methods 40 samples were prepared for PMMA (SR Triplex Hot), polyamide (Deflex) and 3D printed resin (PowerResins Denture) materials and divided into four subgroups for cleansers (Aktident™, Protefix™, Corega™ tablets and distilled water) (n = 5). After the surface preparations were completed, the samples were immersed separately in tubes containing the prepared microorganism suspension and incubated at 37˚C for 24 h. After the incubation, the samples were kept in the cleanser solutions. The samples were then transferred to sterile saline tubes. All the tubes were vortexed and 10 µl was taken from each of them. Sheep blood agar was inoculated for colony counting. The inoculated plates were incubated for 48 h for S. mutans and 24 h for C. albicans. After incubation, colonies observed on all plates were counted. Statistical analyses were done with three-way ANOVA and Tukey’s multiple comparison test. Results Polyamide material registered the highest colony count of S. mutans, whereas PMMA registered the lowest. Significant differences in S. mutans adherence (p = 0.002) were found between the three denture base materials, but no such difference in C. albicans adherence (p = 0.221) was identified between the specimens. All three cleanser tablets eliminated 98% of S. mutans from all the material groups. In all these groups, as well, the antifungal effect of Corega™ on C. albicans was significantly higher than those of the other two cleanser tablets. Conclusions According to the study’s results, it may be better to pay attention to surface smoothness when using polyamide material to prevent microorganism retention. Cleanser tablets are clinically recommended to help maintain hygiene in removable denture users, especially Corega tablets that are more effective on C. albicans.

Abstract Background Endogenous endophthalmitis (EE) is a rare but highly destructive eye emergency secondary to systemic infection. Acute endophthalmitis can lead to irreversible vision impairment or even loss of the whole eye, unless being diagnosed and treated promptly. Case presentation This study reports three typical EE cases of endogenous endophthalmitis secondary to different severe systemic diseases. Patients were recruited from the Department of ophthalmology at Zhongnan hospital of Wuhan University and the Department of ophthalmology at the Second Affiliated Hospital of Fujian Medical University. Patients were followed up for up to 60 days. Among these cases, the eye symptoms is the initial manifestations while secondary to original different special systemic conditions. Patients have been treated under dynamically prompt response undergoing systemic treatment and eye treatment at the same time. Best corrected visual acuity were 20/40, 20/60 and light perception during follow-up evaluation. Conclusions Our observation suggest that prompt identification and treatment could save patients’ vision from EE.

Background: In this study, the antimicrobial activity of three different cleanser tablets on S. mutans and C. albicans adhesion to PMMA, polyamide and 3D printed resin was investigated. Methods: 40 samples were prepared for PMMA (SR Triplex Hot), polyamide (Deflex) and 3D printed resin (PowerResins Denture) materials and divided into four subgroups for cleansers (Aktident™, Protefix™, Corega™ tablets and distilled water) (n = 5). After the surface preparations were completed, the samples were immersed separately in tubes containing the prepared microorganism suspension and incubated at 37˚C for 24 h. After the incubation, the samples were kept in the cleanser solutions. The samples were then transferred to sterile saline tubes. All the tubes were vortexed and 10 µl was taken from each of them. Sheep blood agar was inoculated for colony counting. The inoculated plates were incubated for 48 h for S. mutans and 24 h for C. albicans. After incubation, colonies observed on all plates were counted. Statistical analyses were done with three-way ANOVA and Tukey's multiple comparison test. Results: Polyamide material registered the highest colony count of S. mutans, whereas PMMA registered the lowest. Significant differences in S. mutans adherence (p = 0.002) were found between the three denture base materials, but no such difference in C. albicans adherence (p = 0.221) was identified between the specimens. All three cleanser tablets eliminated 98% of S. mutans from all the material groups. In all these groups, as well, the antifungal effect of Corega™ on C. albicans was significantly higher than those of the other two cleanser tablets. Conclusions: According to the study's results, it may be better to pay attention to surface smoothness when using polyamide material to prevent microorganism retention. Cleanser tablets are clinically recommended to help maintain hygiene in removable denture users, especially Corega tablets that are more effective on C. albicans. [ABSTRACT FROM AUTHOR]

Candida albicans, a pathogenic fungus, poses a significant threat, particularly in individuals with compromised immune systems, leading to elevated mortality rates. The problem is exacerbated by their ability to form biofilms on medical devices, such as catheters, thereby resisting treatments. To tackle this challenge, we have developed an innovative approach involving the detection and combatting of C. albicans biofilm and its associated stages in the presence of a unique antimicrobial nanocomposite (ZnO/Ag/RGO) coating. Microscopic assessments reveal the nanocomposite's exceptional inhibitory impact on C. albicans cells, demonstrating its efficacy. Time-kinetic experiments further elucidate the restraining effects of ZnO/Ag/RGO coatings on C. albicans biofilm formation over intervals. The absence of hypha structures on nanocomposite-coated surfaces was also noted. A concentration-dependent decrease in cell adhesion further validates the potency of the nanocomposite. To substantiate our findings, we employed advanced techniques such as electrochemical impedance spectroscopy (EIS) and cyclic voltage spectrometry (CV) for real-time electronic monitoring of biofilm dynamics. These experiments revealed differences in the time- and concentration-dependent curves. While the concentration-dependent curve maintained linearity, the time-dependent graph portrayed a distinct expression, probably due to cell association. This work stands out as one of the few endeavors seeking to map events within the biofilm matrix in response to an external agent, providing valuable insights into the interplay between ZnO, Ag, and RGO and biofilm dynamics. Our present approach, combining microscopy and electrochemical data, holds promise in contributing to the development of sensing strategies for microbial biofilms and their inhibition. [ABSTRACT FROM AUTHOR]

Fungal resistance and the environmental degradation posed by conventional fungicides necessitate the need to develop new antifungal agents that can inhibit fungal growth. This study sought to prepare biofungicides by leveraging on the antifungal activity of copper‐metal organic framework (Cu‐MOF) and dialdehyde chitosan (Cs) isolated from black soldier flies (BSF). Cs were oxidized using potassium periodate to obtain dialdehyde Cs (OCs) and thereafter, Cu‐MOF was loaded resulting in Cu‐MOF‐OCs. Fourier Transform Infrared spectrophotometer (FT‐IR) and powder X‐ray diffraction (XRD) confirmed the presence of carbonyl functional groups in OCs and sharp intense peaks associated with Cu that interacted. The changes in surface morphology and the presence of Cu in the MOFs as obtained with Scanning Electron Microscope‐ Energy Dispersive X‐ray (SEM‐EDX), indicated the successful loading of Cu‐MOF on the oxidized Cs. Thermogravimetric analysis (TGA) showed a loss of approximately 31.51 % of the loaded OCs and 40.72 % framework around ∼200 to ∼300 °C and ∼410 to ∼475 °C respectively. The antifungal activity of OCs, Cu‐MOF, and Cu‐MOF‐OCs against Aspergillus brasiliensis and Candida albicans was performed using the plate count method and the results suggested that MOF modulated the antifungal activity exerted by the OCs. [ABSTRACT FROM AUTHOR]

Background: Endogenous endophthalmitis (EE) is a rare but highly destructive eye emergency secondary to systemic infection. Acute endophthalmitis can lead to irreversible vision impairment or even loss of the whole eye, unless being diagnosed and treated promptly. Case presentation: This study reports three typical EE cases of endogenous endophthalmitis secondary to different severe systemic diseases. Patients were recruited from the Department of ophthalmology at Zhongnan hospital of Wuhan University and the Department of ophthalmology at the Second Affiliated Hospital of Fujian Medical University. Patients were followed up for up to 60 days. Among these cases, the eye symptoms is the initial manifestations while secondary to original different special systemic conditions. Patients have been treated under dynamically prompt response undergoing systemic treatment and eye treatment at the same time. Best corrected visual acuity were 20/40, 20/60 and light perception during follow-up evaluation. Conclusions: Our observation suggest that prompt identification and treatment could save patients' vision from EE. [ABSTRACT FROM AUTHOR]

Despite significant progress in the development of phototherapy drugs, it is widely recognized that natural products remain the primary source of new photoactive compounds. Exploring uncharted flora in the east‐central region of Argentina may offer a vast array of opportunities to isolate new photoactive molecules or plant extracts with high potential for use in antimicrobial photodynamic therapy (aPDT) against Candida albicans. To assess the photofungicidal potential of T. sinuata ("contrayerba") against C. albicans, the extracts underwent spectroscopic and chromatographic analysis, resulting in the identification of furanocoumarin metabolites with similar spectrophotometric properties in all extracts. The extract profiles were created using UHPLC‐DAD, and seven furanocoumarins (FCs) were detected. The highest photoinactivation against C. albicans was observed for dicholormethanic extracts (MFC = 62.5 μg/mL), equal to xanthotoxin employed as a positive control. Furthermore, we determine that photochemical mechanisms dependent on oxygen (type I and type II processes) and mechanisms independent of oxygen (photoadduct formation) are involved in the death of these yeasts. These results support the use of native plants of the east‐central region of Argentina as potent sensitizers for aPDT and suggest that they can replace xanthotoxin in treating superficial yeast infections of the skin. [ABSTRACT FROM AUTHOR]

Candida albicans Prn1 is a protein with an unknown function similar to mammalian Pirin. It also has orthologues in other pathogenic fungi, but not in Saccharomyces cerevisiae. Prn1 highly increases its abundance in response to H2O2 treatment; thus, to study its involvement in the oxidative stress response, a C. albicans prn1∆ mutant and the corresponding wild-type strain SN250 have been studied. Under H2O2 treatment, Prn1 absence led to a higher level of reactive oxygen species (ROS) and a lower survival rate, with a higher percentage of death by apoptosis, confirming its relevant role in oxidative detoxication. The quantitative differential proteomics studies of both strains in the presence and absence of H2O2 indicated a lower increase in proteins with oxidoreductase activity after the treatment in the prn1∆ strain, as well as an increase in proteasome-activating proteins, corroborated by in vivo measurements of proteasome activity, with respect to the wild type. In addition, remarkable differences in the abundance of some transcription factors were observed between mutant and wild-type strains, e.g., Mnl1 or Nrg1, an Mnl1 antagonist. orf19.4850, a protein orthologue to S. cerevisiae Cub1, has shown its involvement in the response to H2O2 and in proteasome function when Prn1 is highly expressed in the wild type. [ABSTRACT FROM AUTHOR]

Candida (C.) infections represent a serious health risk for people affected by inflammatory bowel disease. An important fungal virulence factor is the capacity of the fungus to form biofilms on the colonized surface of the host. This research study aimed to determine the effect of a C. tropicalis and C. albicans co-infection on dextran sodium sulfate (DSS)-induced colitis in mice. The colitis severity was evaluated using histology and a colonoscopy. The mice were mono-inoculated with C. albicans or C. tropicalis or co-challenged with both species. The mice were administered 3% DSS to induce acute colitis. The biofilm activity was assessed using (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl] 2H-tetrazoliumhydroxide (XTT) and dry-weight assays. The abundance of C. albicans in the colon tissues was assessed by immunohistochemistry. The co-challenged mice showed a decreased colitis severity compared to the mono-inoculated mice. The dry-weight assay demonstrated a marked decrease in C. albicans biofilm production in a C. albicans culture incubated with C. tropicalis supernatant. Immunohistochemical staining showed that C. albicans was more abundant in the mucosa of C. albicans mono-inoculated mice compared to the co-inoculated group. These data indicate an antagonistic microbial interaction between the two Candida species, where C. tropicalis may produce molecules capable of limiting the ability of C. albicans to adhere to the host intestinal surface, leading to a reduction in biofilm formation. [ABSTRACT FROM AUTHOR]

Candida albicans is a prevalent fungal pathogen that displays antibiotic resistance. The polyene antifungal amphotericin B (AmB) has been the gold standard because of its broad antifungal spectra, and its liposomal formulation, AmBisome, has been used widely and clinically in treating fungal infections. Herein, we explored enhancing the antifungal activity of AmBisome by integrating a small chitin-binding domain (LysM) of chitinase A derived from Pteris ryukyuensis. LysM conjugated with a lipid (LysM–lipid) was initially prepared through microbial transglutaminase (MTG)-mediated peptide tag-specific conjugation of LysM with a lipid–peptide substrate. The AmBisome formulation modified with LysM–lipid conjugates had a size distribution that was comparable to the native liposomes but an increased zeta potential, indicating that LysM–lipid conjugates were anchored to AmBisome. LysM–lipid-modified AmBisome exhibited long-term stability at 4 °C while retaining the capacity to bind chitin. Nevertheless, the antifungal efficacy of LysM–lipid-modified AmBisome against C. albicans was modest. We then redesigned a new LysM–lipid conjugate by introducing a peptide linker containing a thrombin digestion (TD) site at the C-terminus of LysM (LysM–TD linker–lipid), thereby facilitating the liberation of the LysM domain from AmBisome upon the addition of thrombin. This new AmBisome formulation anchored with LysM–TD linker–lipid exhibited superior performance in suppressing C. albicans growth in the presence of thrombin compared with the LysM–lipid formulation. These results provide a platform to design stimuli-responsive AmBisome formulations that respond to external environments and thus advance the treatment of pathogenic fungi infections. [ABSTRACT FROM AUTHOR]

Purpose of Review: Farnesol (FOH) is a quorum-sensing molecule with potential as an antifungal drug. Given the growing concern about fungal drug resistance, exploring new solutions is crucial. Therefore, summarizing the antifungal activity of FOH is expected to be the basis for further FOH research and application. Herein, we reviewed the in vitro and in vivo antifungal efficacy of FOH alone and in combination with conventional antifungal drugs, as well as its mechanisms of action. Furthermore, we discussed the prospects and challenges of the FOH application in detail. Recent Findings: Recent studies have revealed that FOH can target various aspects, such as reactive oxygen species production, induction of apoptosis, and modulation of virulence factors, to inhibit fungal growth and reduce fungal pathogenicity, thereby exerting its antifungal activity. Furthermore, FOH can suppress resistance-associated genes, such as those of biofilm and ergosterol, so as to enhance the fungicidal effectiveness of conventional antifungal drugs. However, the action mechanism of FOH on drug efflux pumps remains unclear and warrants further investigation. Summary: FOH can prevent and treat fungal infections. It exerts significant antimicrobial effects on fungal planktonic and biofilm cells, enhances the antimicrobial efficacy of conventional antifungal drugs, and reverses and reduces fungal drug resistance. However, further in vitro and in vivo studies are needed to assess the safety of FOH due to potential adverse effects on immune cells and other factors. [ABSTRACT FROM AUTHOR]

Fibrous cellulose acetate (CA) materials loaded with rosmarinic acid (RA) were successfully created by one-pot electrospinning. In order to improve the water solubility of the polyphenolic acid and to facilitate its release from the fibrous materials, the non-ionic water-soluble polyethylene glycol (PEG) was added. Detailed characterization of the fabricated fibrous CA/RA and CA/PEG/RA materials was performed using scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), UV-Vis spectroscopy and water contact angle analysis. The optimal ratio between CA, RA and PEG for preparation of defect-free and uniform fibers was accomplished by varying their concentrations. Furthermore, the incorporation of the PEG improved the hydrophilicity and wettability of the fibrous CA materials. Moreover, PEG facilitated the RA release and over 360 min, the amount released from fibrous CA/PEG/RA fibers was 91%, while that released from CA/RA materials was 53%. Both of the RA-containing fibrous materials, with and without PEG, manifested high antioxidant activity as determined by the DPPH free radical-scavenging method. In addition, the electrospun CA/PEG/RA materials displayed good antifungal activity against C. albicans. These features make the fibrous CA/PEG/RA materials promising candidates for treatment of wound infections. [ABSTRACT FROM AUTHOR]

Dental caries remains a prevalent concern among children globally and is associated with Candida sp. Some researchers have suggested probiotic supplements as a possible solution for reducing dental caries. A study conducted in Tamil Nadu focused on collecting 80 dental caries samples from both males and females, obtained from two different locations. The samples underwent processing using the spread plate technique, followed by anticandidal activity assessments. Through ITS sequence analysis, candida strains were identified, including C. albicans (DDGRPO1, DDGRPO2). The study specifically investigated the ability of the probiotic bacterial strain Lb. fermentum cell-free filtrate to inhibit C. albicans. The research revealed that Lb. fermentum probiotics effectively inhibited the growth of C. albicans DDGRP01, displaying strong antifungal activity against Candida sp. (98%). While these results are promising, it is worth mentioning the increasing interest in exploring innovative alternatives to probiotic-based treatments. This avenue of research offers potential for a more comprehensive approach to addressing this issue. Notably, Lb. fermentum, derived from the human oral cavity, emerges as a significant postbiotic candidate for dental prophylaxis, indicating a hopeful direction for future studies. [ABSTRACT FROM AUTHOR]

We assessed the effect of different compositions and concentrations of two etidronate-containing irrigants on the antibacterial activity of sodium hypochlorite (SH) against Enterococcus faecalis and Candida albicans in vitro. Pure cultures of C. albicans and E. faecalis were isolated from root canal samples. The disc diffusion method was used to compare the antibacterial effect of pure SH and SH mixed with 9%, 15%, and 18% etidronate of two manufactures (dual rinse (DR); IsraDent (ID)) and EDTA. The pH and temperature of the solutions were measured immediately after mixing and within 40 min. The ANOVA revealed a significant influence of the type of irrigating solution on the C. albicans and E. faecalis inhibition zone diameters that ranged from 6.6 to 51.6 mm and from 6.4 to 12.4 mm, respectively. SH with DR 9% exhibited the highest effect against C. albicans. The antifungal activity of the other irrigants was SH = SH + DR15% = SH + DR18% = SH + ID9% > SH + EDTA > SH + ID15% > SH + ID18%. No significant differences in the anti-E. faecalis effect were revealed between the tested solutions except for the mixtures of SH and 15% and 18% ID, which exhibited no antiseptic effect. There was a strong positive correlation between antiseptic activity against both microorganisms and the pH values of the tested solutions. In conclusion, most etidronate formulations did not significantly hamper sodium hypochlorite activity against C. albicans and E. faecalis. The effect was concentration- and manufacturer-dependent. [ABSTRACT FROM AUTHOR]

Abstract Objectives Guided bone regeneration (GBR) is a core procedure used to regenerate bone defects. The aim of the study was to investigate the adherence of Candida albicans on six commercially available polytetrafluoroethylene (PTFE) membranes used in GBR procedures and the subsequent clinical consequences. Materials and Methods Six commercially available PTFE membranes were tested. Two of the membranes had a textured surface and the other four a plane, nontextured one. C. albicans (ATCC 24433) was cultured for 24 h, and its cell surface hydrophobicity was assessed using a modified method. C. albicans adhesion to membrane discs was studied by scanning electron microscopy (SEM) and real‐time polymerase chain reaction (PCR). Results C. albicans was found to be hydrophobic (77.25%). SEM analysis showed that C. albicans adherence to all membranes examined was characterized by patchy, scattered, and small clustered patterns except for one nontextured membrane with a most rough surface in which a thick biofilm was observed. Real‐time PCR quantification revealed significantly greater adhesion of C. albicans cells to PTFE membranes than the control membrane (p ≤ .001) with the membranes having a textured surface exhibiting the highest count of 2680 × 104 cells/ml compared to the count of 707 × 104 cells/mL on those with a nontextured one (p ≤ .001). One membrane with nontextured surface, but with most rough surface was found to exhibit the highest count of 3010 × 104 cells/ml (p ≤ .05). Conclusion The results of this study indicate that C. albicans adhesion on membranes' surfaces depends on the degree of surface roughness and/or on the presence of a texture. Textured PTFE membranes and/or membranes high roughness showed significantly more adhered C. albicans cells. These findings can impact the surgeon's choice of GBR membrane and postoperative maintenance.

The rise in drug-resistant fungal infections poses a significant public health concern, necessitating the development of new antifungal therapies. We aimed to address this challenge by targeting a yeast casein kinase of Candida albicans for antifungal drug development. The compound library contained 589 chemical structures similar to the previously identified kinase inhibitor GW461484A. Through virtual screening, four compounds with the PubChem IDs 102583821, 12982634, 102487860, and 86260205 were selected based on their binding energies. Hydrophobic bonds and van der Waals interactions stabilised the docked complexes. Comprehensive interaction studies and a 200-nanosecond molecular dynamics simulation suggested that these molecules can maintain stable interactions with the target, as evidenced by satisfactory RMSD and RMSF values. The Rg-RMSD-based Free Energy Landscape of these complexes indicated thermodynamic stability due to the presence of conformers with global minima. These promising findings highlight the potential for developing novel antifungal therapies targeting Yck2 in C. albicans. Further experimental validation is required to assess the efficacy of these compounds as antifungal agents. This research provides a significant step towards combating antifungal resistance and opens up a new avenue for drug discovery.

Copper oxide nanoparticles (CuO NPs) were synthesized using ayurvedic medicine septilin. The septilin-mediated CuO NPs were characterized using UV–Vis, fourier-transform infrared spectroscopy, X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscope (TEM). The average particle size of CuO NPs was 8 nm as evident from TEM. Minimum inhibitory concentration of CuO NPs against Escherichia coli, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans was found in the range of 1–2.5 mg·mL−1. CuO NPs dose-dependently decreased the biofilm formation from 0.0315 to 2 mg·mL−1, at the highest dose of 2 mg·mL−1 of CuO NPs; 92.91%, 79.84%, and 71.57% decrease in biofilm was observed for P. aeruginosa, MRSA, and C. albicans, respectively. Down-regulation of biofilm upon treatment with nanoparticles (NPs) was also observed by SEM analysis. SEM analysis also showed the change in morphological structure, and deformities in bacterial and fungal cells upon treatment of NPs. Furthermore, the anticancer efficacy of NPs was assessed using colon cancer (HCT-116). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay clearly showed the anticancer potential of NPs, as the concentration of CuO NPs increased, the number of viable cells decreased. The produced CuO NPs have promise for future investigations in many biological and therapeutic domains, including the treatment of microbial biofilm infections, as well as the inhibition of cancer cell growth.

The growing emergence of resistance mechanisms and side effects associated with antifungal agents highlight the need for alternative therapies. This study aims to investigate the antifungal potential of ozonated extra-virgin olive oil (EOO) against Candida albicans, with the goal of developing eco-friendly and highly effective treatments based on natural products. Antifungal activity was evaluated via cell viability and biofilm formation assays using Crystal Violet and Sytox green staining. The results showed that EOO reduced C. albicans viability in a dose-dependent manner, achieving over 90% cell death at a 3% (v/v) concentration. Transmission Electron Microscopy (TEM) revealed cell wall structural damage, and ROS levels increased by approximately 60% compared to untreated controls within 10 min of treatment. Additionally, the expression of autophagy-related genes atg-7 and atg-13was upregulated by 2- and 3.5-fold, respectively, after 15 min, suggesting a stress-induced cell death response. EOO also significantly inhibited hyphal formation and biofilm development, thus reducing C. albicans pathogenicity while preserving cell biocompatibility. EOO antifungal activity was also observed in the case of Candida glabrata. In conclusion, ozonated olive oil demonstrates potent antifungal activity against C. albicans by reducing cell viability, inhibiting hyphal and biofilm formation, and triggering oxidative stress and autophagy pathways. These findings position EOO as a promising alternative therapy for fungal infections.

A novel decalin derivative, trans-1-oxo-2,4-diacetylaminodecalin (1) with anti-Candida activity, had been isolated from Streptomyces chrestomyceticus strain ADP4. The structure of the compound was determined from the analysis of spectral data (LCMS/MS, UV, FTIR, 1D- and 2D-NMR). The anti-Candida activity of 1 was specific to Candida albicans and Candida auris. Further, it displayed inhibition of the early-stage biofilm of C. albicans. In-silico analysis of the compound revealed its drug likeness properties without any violations and PAINS alert when investigated for ADME properties. Along with the overall bioavailability, compound 1 did not show any predicted bioaccumulation and mutagenicity in the analysis by TEST software. Non-cytotoxic property was further confirmed by in-vitro assay on the HepG2 cell line. [ABSTRACT FROM AUTHOR]

Emerging life-threatening multidrug-resistant (MDR) species such as the C. haemulonii species complex, Clavispora lusitaniae (sin. C. lusitaniae), and other Candida species are considered as an increasing risk for human health in the near future. (1) Background: Many studies have emphasized that the increase in drug resistance can be associated with several virulence factors in Candida and its knowledge is also essential in developing new antifungal strategies. (2) Methods: Hydrophobicity, adherence, biofilm formation, lipase activity, resistance to osmotic stress, and virulence 'in vivo' on G. mellonella larvae were studied in isolates of C. haemulonii, C. albicans, and C. lusitaniae with low susceptibility and resistance to fluconazole and amphotericin B. (3) Results: Intra- and interspecies variability were observed. C. haemulonii showed high hydrophobicity and the ability to adhere to and form biofilm. C. lusitaniae was less hydrophobic, was biofilm-formation-strain-dependent, and did not show lipase activity. Larvae inoculated with C. albicans isolates displayed significantly higher mortality rates than those infected with C. haemulonii and C. lusitaniae. (4) Conclusions: The ability to adhere to and form biofilms associated with their hydrophobic capacity, to adapt to stress, and to infect within an in vivo model, observed in these non-wild-type Candida and Clavispora isolates, shows their marked virulence features. Since factors that define virulence are related to the development of the resistance of these fungi to the few antifungals available for clinical use, differences in the physiology of these cells must be considered to develop new antifungal therapies. [ABSTRACT FROM AUTHOR]

Background: Candida spp are the most common opportunistic fungal pathogen causing infections in humans. In recent times, prevalence of candidiasis is on the rise due to indiscriminate use of antibiotics and steroids, AIDS and other immunosuppressive conditions. Some Candida spp. are intrinsically resistant to commonly prescribed antifungal drugs leading to treatment failure and episodes of recurrences. Moreover, emerging antifungal resistance in various Candida species has made the situation grievous. This mandates early identification and determination of antifungal susceptibility pattern of various Candida spp. Aim: To characterize Candida isolates and to determine their antifungal susceptibility pattern from various clinical samples at a tertiary care hospital. Material and methods: All isolates of Candida spp. isolated from various clinical specimens were included in this study. Speciation of Candida spp. Were performed by germ tube test, HiChrome agar, cornmeal agar and carbohydrate fermentation and assimilation. Antifungal susceptibility testing was done as per standard guidelines. Results: Out of total 229 Candida isolates, 28.8% were C. albicans and 71.2% were NAC. Among 163 non-albicans Candida spp.; C. tropicalis (103) was the most common isolate followed by C. glabrata (34), C. parapsilosis (19) and C. krusei (07). Susceptibility towards Fluconazole was found to be more in C. albicans as compared to NAC spp. In this study, NAC species also showed relatively reduced susceptibility to Amphotericin B. Conclusion: Prevalence of candidiasis is alarmingly increasing leading to significant morbidity and mortality. Various Candida spp. show difference in antifungal susceptibility attributing to treatment failure and episodes of recurrences. Early identification of Candida spp. and determination of their antifungal susceptibility pattern are crucial in selecting most appropriate antifungal drug for patient treatment. [ABSTRACT FROM AUTHOR]

Pathogenic microorganisms such as bacteria, viruses, fungi and protozoa have played a central role in the safety of drinking water, since they spread easily in the water network, constituting a health risk for humans and animals. Currently in water treatments, advanced oxidative processes (AOPs) have been increasing in importance in the microbiological disinfection of water. The present study aimed to inactivate C. albicans, a commensal yeast species in Vertebrates that can cause disease, using AOPs. To achieve this objective, a powerful oxidant (hydrogen peroxide) was combined with UV radiation to promote the inactivation of C. albicans. Initially, the inactivation capacity of the H2O2 was assessed and it was verified that the application of 2.5 mM, 5 mM and 10 mM H2O2 reached a cell reduction of 3 log after 180, 360 and 300 min, respectively. Subsequently, the combination with UV-A radiation (λ = 365 nm) proved to be even more promising, as the H2O2 + UV-A system, using the same H2O2 concentrations, reached an inactivation of 3 log after 240, 180 and 60 min, respectively. These results support that UV-A radiation promotes the generation of hydroxyl radicals, which have a comparatively higher oxidation potential (2.8 eV) to the H2O2 (1.8 eV), responsible for the inactivation of C. albicans cells. Thus, the UV-A/H2O2 process can reduce this microorganism in an aqueous matrix, avoiding potential hazards to human and animal health. [ABSTRACT FROM AUTHOR]

Aim This study aims to incorporate alginate microparticles containing berberine and fluconazole into two different types of pharmaceutical formulations, to subsequently evaluate the antifungal activity against Candida albicans. Methods and Results Alginate microparticles containing BBR (berberine) and FLU (fluconazole) were produced by the spray-drying technique, characterized and incorporated in two pharmaceutical formulations, a vaginal cream and artificial saliva. Broth microdilution, checkerboard, time–kill curve, and scanning electron microscopy were carried out to determine the antifungal effects of BBR and FLU against C. albicans. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of free BBR were 125 μg ml−1. Synergism between BBR and FLU was demonstrated by a fractional inhibitory concentration index (FICI) = 0.0762. The time–kill curve for the combination BBR + FLU showed a more pronounced decrease in fungal growth in comparison to free drugs, and an antibiofilm effect of BBR occurred in the formation and preformed biofilm. Conclusion Alginate microparticles containing BBR and FLU were obtained and incorporated in a vaginal cream and artificial saliva. Both formulations showed good stability, antifungal effects, and organoleptic characteristics, which suggest that BBR–FLU microparticles in formulations have potential as antifungal therapy. [ABSTRACT FROM AUTHOR]

Candida albicans (C. albicans), the most common fungal pathogen, has the ability to form a biofilm, leading to enhanced virulence and antibiotic resistance. Cocultimycin A, a novel antifungal antibiotic isolated from the co-culture of two marine fungi, exhibited a potent inhibitory effect on planktonic C. albicans cells. This study aimed to evaluate the anti-biofilm activity of cocultimycin A against C. albicans and explore its underlying mechanism. Crystal violet staining showed that cocultimycin A remarkably inhibited biofilm formation in a dose-dependent manner and disrupted mature biofilms at higher concentrations. However, the metabolic activity of mature biofilms treated with lower concentrations of cocultimycin A significantly decreased when using the XTT reduction method. Cocultimycin A could inhibit yeast-to-hypha transition and mycelium formation of C. albicans colonies, which was observed through the use of a light microscope. Scanning electron microscopy revealed that biofilms treated with cocultimycin A were disrupted, yeast cells increased, and hypha cells decreased and significantly shortened. The adhesive ability of C. albicans cells treated with cocultimycin A to the medium and HOEC cells significantly decreased. Through the use of a qRT-PCR assay, the expression of multiple genes related to adhesion, hyphal formation and cell membrane changes in relation to biofilm cells treated with cocultimycin A. All these results suggested that cocultimycin A may be considered a potential novel molecule for treating and preventing biofilm-related C. albicans infections. [ABSTRACT FROM AUTHOR]

Candida glabrata and Candida albicans, the most frequently isolated candidiasis species in the world, have developed mechanisms of resistance to treatment with azoles. Among the clinically used antifungal drugs are statins and other compounds that inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), resulting in decreased growth and ergosterol levels in yeasts. Ergosterol is a key element for the formation of the yeast cell membrane. However, statins often cause DNA damage to yeast cells, facilitating mutation and drug resistance. The aim of the current contribution was to synthesize seven series of compounds as inhibitors of the HMGR enzyme of Candida ssp., and to evaluate their effect on cellular growth, ergosterol synthesis and generation of petite mutants of C. glabrata and C. albicans. Compared to the reference drugs (fluconazole and simvastatin), some HMGR inhibitors caused lower growth and ergosterol synthesis in the yeast species and generated fewer petite mutants. Moreover, heterologous expression was achieved in Pichia pastoris, and compounds 1a, 1b, 6g and 7a inhibited the activity of recombinant CgHMGR and showed better binding energy values than for α-asarone and simvastatin. Thus, we believe these are good candidates for future antifungal drug development. [ABSTRACT FROM AUTHOR]