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Vaginal colonization by fungi may elicit genital inflammation and enhance the risk of adverse reproductive health outcomes, such as HIV acquisition. Cross-sectional studies have linked fungi with an absence of bacterial vaginosis (BV), but it is unclear whether shifts in vaginal bacteria alter the abundance of vaginal fungi. Vaginal swabs collected following topical metronidazole treatment for BV during the phase 2b, placebo-controlled trial of LACTIN-V, a Lactobacillus crispatus-based live biotherapeutic, were assayed with semi-quantitative PCR for the relative quantitation of fungi and key bacterial species and multiplex immunoassay for immune factors. Vaginal fungi increased immediately following metronidazole treatment for BV (adjusted P = 0.0006), with most of this increase attributable to Candida albicans. Vaginal fungi were independently linked to elevated levels of the proinflammatory cytokine interleukin (IL) 17A, although this association did not remain significant after correcting for multiple comparisons. Fungal relative abundance by semi-quantitative PCR returned to baseline levels within 1 month of metronidazole treatment and was not affected by LACTIN-V or placebo administration. Fungal abundance was positively associated with Lactobacillus species, negatively associated with BV-associated bacteria, and positively associated with a variety of proinflammatory cytokines and chemokines, including IL-17A, during and after study product administration. Antibiotic treatment for BV resulted in a transient expanded abundance of vaginal fungi in a subset of women which was unaffected by subsequent administration of LACTIN-V. Vaginal fungi were positively associated with Lactobacillus species and IL-17A and negatively associated with BV-associated bacteria; these associations were most pronounced in the longer-term outcomes.IMPORTANCEVaginal colonization by fungi can enhance the risk of adverse reproductive health outcomes and HIV acquisition, potentially by eliciting genital mucosal inflammation. We show that standard antibiotic treatment for bacterial vaginosis (BV) results in a transient increase in the absolute abundance of vaginal fungi, most of which was identified as Candida albicans. Vaginal fungi were positively associated with proinflammatory immune factors and negatively associated with BV-associated bacteria. These findings improve our understanding of how shifts in the bacterial composition of the vaginal microbiota may enhance proliferation by proinflammatory vaginal fungi, which may have important implications for risk of adverse reproductive health outcomes among women.

Introduction: A tension empyema, in which purulent material accumulates in the chest cavity and leads to cardiopulmonary dysfunction, is a rare complication of empyemas. Moreover, fungal empyemas that grow Candida albicans and cause tension physiology have not yet been previously described.Case Report: In this report, we present an immunocompetent 30-year-old male who presented to the emergency department with worsening shortness of breath and was found to have a left-sided fungal empyema causing tension physiology. Left chest thoracostomy yielded approximately 4 liters of purulent fluid. Pleural cultures eventually grew C albicans, and after antifungal therapy, surgical decortication of the lung, and a prolonged intensive care unit stay, the patient was discharged home in stable condition.Conclusion: While mortality from C albicans empyemas that cause respiratory compromise is exceedingly high, our case highlights that aggressive management with rapid chest thoracostomy and antifungal therapy can lead to a favorable outcome.

Purpose: To evaluate the effect of adding tea tree oil to denture liners on Candida albicans and bond strength to the acrylic denture base. Materials and Methods: Disc-shaped specimens were fabricated from silicone-based resilient liner (Tokuyama, Molloplast), acrylic-based hard liner (GC Reline), and acrylic-based soft liner (Visco-gel). Tea tree oil (TTO) was incorporated into the liners at varying concentrations (0% [control], 2%, 5%, 8%). C albicans were counted by viable colony count, and optical density (OD) was measured with a spectrophotometer. The tensile strength to heat polymerized acrylic denture base was measured in a universal testing machine. The compliance of the data to the distribution of normality was evaluated using the Shapiro Wilk test. Two-way ANOVA, Bonferroni correction, and paired sample t test were performed (α = .05). Results: The addition of TTO into liners provided a significant decrease in the OD values (P < .001). The control groups of the liners presented the highest colony counts, whereas increasing TTO decreased the results (P < .01). According to tensile bond strength test, 8% TTO addition resulted in a significant decrease for Tokuyama (P < .01) and Molloplast liners (P < .05), while 2% TTO resulted in significance for GC Reline (P < .001). Conclusions: Denture liners containing increasing percentages of TTO presented lower amounts of C albicans colonies and decreased bond strength to the denture bases. When using TTO for its antifungal properties, the amount added should be carefully selected because the tensile bond strength may be affected. [ABSTRACT FROM AUTHOR]

Patients with decreased levels of CD18 (β2 integrins) suffer from life-threatening bacterial and fungal infections. CD11b, the α subunit of integrin CR3 (CD11b/CD18, αMβ2), is essential for mice to fight against systemic Candida albicans infections. Live elongating C. albicans activates CR3 in immune cells. However, the hyphal ligands that activate CR3 are not well defined. Here, we discovered that the C. albicans Als family proteins are recognized by the I domain of CD11b in macrophages. This recognition synergizes with the β-glucan-bound lectin-like domain to activate CR3, thereby promoting Syk signaling and inflammasome activation. Dectin-2 activation serves as the outside-in signaling for CR3 activation at the entry site of incompletely sealed phagosomes, where a thick cuff of F-actin forms to strengthen the local interaction. In vitro, CD18 partially contributes to IL-1β release from dendritic cells induced by purified hyphal Als3. In vivo, Als3 is vital for C. albicans clearance in mouse kidneys. These findings uncover a novel family of ligands for the CR3 I domain that promotes fungal clearance.

Rezafungin is a long-acting, intravenously administered echinocandin for the treatment of candidemia and invasive candidiasis (IC). Non-inferiority of rezafungin vs caspofungin for the treatment of adults with candidemia and/or IC was demonstrated in the Phase 3 ReSTORE study based on the primary endpoints of day 14 global cure and 30-day all-cause mortality. Here, an analysis of ReSTORE data evaluating efficacy outcomes by baseline Candida species is described. Susceptibility testing was performed for Candida species using the Clinical and Laboratory Standards Institute reference broth microdilution method. There were 93 patients in the modified intent-to-treat population who received rezafungin; 94 received caspofungin. Baseline Candida species distribution was similar in the two treatment groups; C. albicans (occurring in 41.9% and 42.6% of patients in the rezafungin and caspofungin groups, respectively), C. glabrata (25.8% and 26.6%), and C. tropicalis (21.5% and 18.1%) were the most common pathogens. Rates of global cure and mycological eradication at day 14 and day 30 all-cause mortality by Candida species were comparable in the rezafungin and caspofungin treatment groups and did not appear to be impacted by minimal inhibitory concentration (MIC) values for either rezafungin or caspofungin. Two patients had baseline isolates with non-susceptible MIC values (both in the rezafungin group: one non-susceptible to rezafungin and one to caspofungin, classified as intermediate); both were candidemia-only patients in whom rezafungin treatment was successful based on the day 30 all-cause mortality endpoint. This analysis of ReSTORE demonstrated the efficacy of rezafungin for candidemia and IC in patients infected with a variety of Candida species.

The tropical marine cyanobacterium Moorena producens JHB is a prolific source of secondary metabolites with potential biomedical utility. Previous studies on this strain led to the discovery of several novel compounds such as hectochlorins and jamaicamides. However, bioinformatic analyses of its genome indicate the presence of numerous cryptic biosynthetic gene clusters that have yet to be characterized. To potentially stimulate the production of novel compounds from this strain, it was cocultured with Candida albicans. From this experiment, we observed the increased production of a new compound that we characterize here as hectoramide B. Bioinformatic analysis of the M. producens JHB genome enabled the identification of a putative biosynthetic gene cluster responsible for hectoramide B biosynthesis. This work demonstrates that coculture competition experiments can be a valuable method to facilitate the discovery of novel natural products from cyanobacteria.

Background and objectives: Mineral Trioxide Aggregate (MTA) is one of the main retrograde filling materials that is used today as a root end filling material and perforation repair material. This study was conducted with the aim of investigating the antibacterial and antifungal properties of four types of bio-ceramic materials, AGM MTA, Ortho MTA, Pro root MTA and Cem cement for oral and dental health. Methods: In this study, the antibacterial activity of four types of bio-ceramic materials against two bacterial strains of Enterococcus faecalis (ATTC 29212), Escherichia coli (ATTC 35318) and antifungal activity against Candida albicans (ATTC 10231) were investigated using the well diffusion method. Results: In the context of the relationship between the type of microorganism and the diameter of the growth inhibitory zone for each type of bio-ceramic material, there was no significant difference for Enterococcus faecalis, and a significant difference was observed for Escherichia coli and Candida albicans (p < 0.05). Conclusion: The results show that each of the bio-ceramic materials AGM, Pro root, Cem cement and Ortho have antibacterial and antifungal properties. AGM MTA bio-ceramic material on Candida albicans fungus and Ortho MTA bio-ceramic material had the most effect on Escherichia coli bacteria. Therefore, the mentioned bio-ceramic materials can play a significant role in oral and dental health by providing a suitable material for restoration. [ABSTRACT FROM AUTHOR]

Background Vulvovaginal candidiasis (VVC) is a condition that impacts women from various ethnic backgrounds and social strata. The precise epidemiology of the disease is difficult to determine due to inconsistent data; however, available information suggests that 70-75% of women will experience VVC at least once in their lifetime. Common symptoms include itching, vaginal discomfort, pain during intercourse, external pain during urination, and unusual discharge. Methods The current study investigates the anticandidal properties of neem (Azadirachta indica) leaf extracts. It compares the anticandidal effects of aqueous and methanolic leaf extracts, as well as green-synthesized silver nanoparticles (AgNPs/SNPs) derived from methanolic neem leaf extract, against Candida albicans isolated from clinical samples of patients with vaginal infection. Results The results showed that AgNPs exhibited a stronger inhibitory effect than both the aqueous and methanol extracts. The methanol extract demonstrated anticandidal activity against C. albicans, while the aqueous extracts had no effect. The anticandidal effect of AgNPs was evaluated using the agar well diffusion method. A topical formulation was created by incorporating the optimized AgNPs into an ointment base, and the in vitro anticandidal assay of this ointment was conducted using the same agar well diffusion method. The inhibitory effectiveness of the AgNPs-infused ointment was found to be comparable to that of a commercial product against Candida albicans. Conclusion Overall, the findings suggest that this formulation has potential anticandidal effects against Candida albicans responsible for Vulvovaginal candidiasis. [ABSTRACT FROM AUTHOR]

Objective: Candida albicans is a common fungal pathogen that triggers complex host defense mechanisms, including coordinated innate and adaptive immune responses, to neutralize invading fungi effectively. Exploring the immune microenvironment has the potential to inform the development of therapeutic strategies for fungal infections. Methods: The study analyzed individual immune cell profiles in peripheral blood mononuclear cells from Candida albicans -infected mice and healthy control mice using single-cell transcriptomics, fluorescence quantitative PCR, and Western blotting. We investigated intergroup differences in the dynamics of immune cell subpopulation infiltration, pathway enrichment, and differentiation during Candida albicans infection. Results: Our findings indicate that infiltration of CD4 + naive cells, regulatory T (Treg) cells, and Microtubules-associated (MT)-associated cells increased after infection, along with impaired T cell activity. Notably, CD4+T cells and plasma cells were enhanced after infection, suggesting that antibody production is dependent on T cells. In addition, we screened 6 hub genes, transcription factor forkhead box protein 3(Foxp3), cytotoxic T-lymphocyte associated protein 4 (CTLA4), Interleukin 2 Receptor Subunit Beta (Il2rb), Cd28, C-C Motif Chemokine Ligand 5 (Ccl5), and Cd27 for alterations associated with CD4+T cell differentiation. Conclusions: These results provide a comprehensive immunological landscape of the mechanisms of Candida albicans infection and greatly advance our understanding of adaptive immunity in fungal infections. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: This systematic review and meta‐analysis aimed to evaluate the clinical and mycological effectiveness of mucoadhesives as vehicles for drugs or natural products in the treatment of oral candidiasis. Materials and methods: The search for articles was carried out in the Medline/PubMed, SCOPUS, EMBASE, Web of Science, Cochrane Library, and SciELO databases before August 2023. We selected the studies, extracted the data, evaluated the study quality, graded the evidence, performed the risk of bias, and carried out meta‐analysis. Results: A total of 389 potentially relevant articles were identified, and 11 studies (1869 participants) met the inclusion criteria of the systematic review. The overall risk of bias was considered low. The most common presentation of mucoadhesives was tablets, with miconazole being the most frequently drug used in the delivery system. Mucoadhesives demonstrated comparable efficacy with topical or systemic antifungal agents, with no significant differences between treatments in terms of clinical (RR = 0.907; 95CI = 0.3–1.297; p = 0.591; I2 = 64.648) or mycological (RR = 0.95; 95CI = 0.667–1.360; p = 0.789; I2 = 73.271) efficacy. Conclusions: Mucoadhesives may be a suitable alternative to conventional treatments, with the advantage of reducing the frequency of application by up to 5 times and the daily dosage by up to 20 times. [ABSTRACT FROM AUTHOR]

Innovative solutions for rapid protection against broad-spectrum infections are very important in dealing with complex infection environments. We utilized a functionally inactive mutated endolysin protein of Streptococcus pneumoniae (ΔA146Ply) to immunize mice against pneumonic infections by multidrug-resistant bacteria, Candida albicans and influenza virus type A. ΔA146Ply protection relied on both immunized tissue-resident and monocyte-derived alveolar macrophages and inhibited infection induced ferroptosis that upregulated expression of GPX4 (glutathione peroxidase) in alveolar macrophages. Ferroptosis resistance endowed macrophages with enhanced phagocytosis by inhibiting lipid peroxidation during infection. Moreover, we demonstrated ΔA146Ply upregulated GPX4 through the TLR4/IRG1/NRF2 pathway. ΔA146Ply also induced ferroptosis inhibition and phagocytosis improvement in human monocytes. This mode of action is a novel and potentially prophylactic and rapid broad-spectrum anti-infection mechanism. Our study provides new insights into protective interventions that act by regulating ferroptosis to improve multiple pathogen resistance via GPX4 targeting. [Display omitted] • ΔA146Ply is a novel prophylactic and broad-spectrum mucosal anti-infective strategy. • GPX4 by ΔA146Ply inhibits ferroptosis and augments phagocytosis in macrophages. • ΔA146Ply upregulates GPX4 through the TLR4/IRG1/NRF2 pathway. • ΔA146Ply inhibits ferroptosis and improves phagocytosis in human monocytes. • New insights into prophylactic anti-infectious prospect by targeting GPX4. [ABSTRACT FROM AUTHOR]

Candidemia leaves a trail of approximately 750,000 cases yearly, with a morbidity rate of up to 30%. While Candida albicans still ranks as the most predominantly isolated Candida species, C. glabrata comes in second, with a death rate of 40–50%. Although infections by Candida spp are commonly treated with azoles, the side effects and rise in resistance against it has significantly limited its clinical usage. The current study aims to address the insolubility of piperine and provide an alternative treatment to Candida infection by formulating a stable piperine-loaded O/W nanoemulsion, comprised of Cremophor RH40, Transcutol HP and Capryol 90 as surfactant, co-surfactant, and oil, respectively. Characterization with zetasizer showed the droplet size, polydispersity (PDI) and zetapotential value of the nanoemulsion to be 24.37 nm, 0.453 and -21.10 mV, respectively, with no observable physical changes such as phase separation from thermostability tests. FTIR peaks confirms presence of piperine within the nanoemulsion and TEM imaging visualized the droplet shape and further confirms the droplet size range of 20–24 nm. The MIC90 value of the piperine-loaded nanoemulsion determined with in vitro broth microdilution assay was approximately 20–50% lower than that of the pure piperine in DMSO, at a range of 0.8–2.0 mg/mL across all Candida spp. tested. Overall, the study showed that piperine can be formulated into a stable nanoemulsion, which significantly enhances its antifungal activity compared to piperine in DMSO. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to develop a double antigen sandwich ELISA (DAgS-ELISA) method for more efficient, accurate, and quantitative detection of total antibodies against Candida albicans enolase1 (CaEno1) for diagnosing invasive candidiasis (IC). Methods: DAgS-ELISA was developed using recombinant CaEno1 and a monoclonal antibody as the standard. Performance evaluation included limit of detection, accuracy, and repeatability. Dynamic changes in antibody levels against CaEno1 in serum from systemic candidiasis mice were analyzed using DAgS-ELISA. Patient serum samples from IC, Candida colonization, bacterial infections, and healthy controls were analyzed with DAgS-ELISA and indirect ELISA. Results: DAgS-ELISA outperformed indirect ELISA in terms of linear range and test background. In systemic candidiasis mice, a distinctive 'double-peak' pattern in dynamic antibody levels was observed. Additionally, there was a high level of consistency in the positive rates of CaEno1 antibodies detected by both DAgS-ELISA and indirect ELISA. While the positivity rates differed among patient groups, no significant variations in antibody levels were detected among the various positive patient groups. Conclusions: DAgS-ELISA offers a reliable novel approach for IC diagnosis, enabling rapid, accurate, and quantitative detection of CaEno1 antibodies. Further validation and optimization are needed for its clinical application and effectiveness. [ABSTRACT FROM AUTHOR]

Boric acid is a broad-spectrum antimicrobial used to treat vulvovaginal candidiasis when patients relapse on the primary azole drug fluconazole. Candida albicans is the most common cause of vulvovaginal candidiasis, colloquially referred to as a "vaginal yeast infection". Little is known about the propensity of C. albicans to develop BA resistance or tolerance (the ability of a subpopulation to grow slowly in high levels of drug). We evolved 96 replicates from eight diverse C. albicans strains to increasing BA concentrations to test the evolvability of BA resistance and tolerance. Replicate growth was individually assessed daily, with replicates passaged when they had reached an optical density consistent with exponential growth. Many replicates went extinct quickly. Although some replicates could grow in much higher levels of BA than the ancestral strains, evolved populations isolated from the highest terminal BA levels (after 11 weeks of passages) surprisingly showed only modest growth improvements and only at low levels of BA. No large increases in resistance or tolerance were observed in the evolved replicates. Overall, our findings illustrate that there may be evolutionary constraints limiting the emergence of BA resistance and tolerance, which could explain why it remains an effective treatment for recurrent yeast infections. [ABSTRACT FROM AUTHOR]

The limited availability of efficient treatments for Candida infections and the increased emergence of antifungal-resistant strains stimulates the search for new antifungal agents. We have previously isolated a sunflower mannose-binding lectin (Helja) with antifungal activity against Candida albicans , capable of binding mannose-bearing oligosaccharides exposed on the cell surface. This work aimed to investigate the biological and biophysical basis of Helja's binding to C. albicans cell wall mannans and its influence on the fungicidal activity of the lectin. We evaluated the interaction of Helja with the cell wall mannans extracted from the isogenic parental strain (WT) and a glycosylation-defective C. albicans with altered cell wall phosphomannosylation (mnn4 ∆ null mutants) and investigated its antifungal effect. Helja exhibited stronger antifungal activity on the mutant strain, showing greater inhibition of fungal growth, loss of cell viability, morphological alteration, and formation of clusters with agglutinated cells. This differential biological activity of Helja was correlated with the biophysical parameters determined by solid phase assays and isothermal titration calorimetry, which demonstrated that the lectin established stronger interactions with the cell wall mannans of the mnn4 ∆ null mutant than with the WT strain. In conclusion, our results provide new evidence on the nature of the Helja molecular interactions with cell wall components, i.e. phosphomannan, and its impact on the antifungal activity. This study highlights the relevance of plant lectins in the design of effective antifungal therapies. [ABSTRACT FROM AUTHOR]

Background/Aims: To determine the clinical features, predisposing factors, and management of infectious keratitis caused by Candida spp. Methods: Retrospective chart review. Results: The medical records of 52 patients (54 eyes) with Candida keratitis were available for statistical analysis. Thinning of the corneal stroma was identified in 34 eyes (63.0%), and corneal perforation occurred in 16 eyes (29.6%). Corneal thinning and perforation were more common in Candida albicans compared with non-albicans (P-val <.001, P =.09, respectively). The most common predisposing factors for Candida keratitis were topical steroid use (21 patients, 40.4%), previous corneal transplantation (17 patients, 32.7%), and preexisting ocular surface disease (15 patients, 28.8%). Fourteen eyes (25.9%) required cyanoacrylate glue application and 10 eyes (18.5%) underwent therapeutic penetrating keratoplasty (TPK). Conclusion: Local immunosuppression and ocular surface disease play an important role in Candida keratitis. C. albicans appears to be more invasive compared with non-albicans spp. [ABSTRACT FROM AUTHOR]

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The increasing prevalence of antibiotic-resistant pathogens necessitates the development of novel antimicrobial agents. Herein, PEGylated konjac gum-supported rosin pentaerythritol nanocomposites (KG/PEG/RE PNCs) were synthesized using an environmentally friendly sonochemical method, aiming to explore their potential antibacterial and antifungal properties against a range of pathogens, including Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Aspergillus brasiliensis, and Staphylococcus aureus. An elaborate investigation into the rheological properties of these PNCs highlighted the dependence of viscosity on synthesis parameters such as RE concentration, sonication time, and KG/RE blend ratio with the Higiro model validated as a suitable mathematical model for defining the intricate relationship between experimental and resulting viscosity of PNCs. The integration of machine learning (ML), particularly polynomial regression, enabled the modeling of the complex dynamics influencing PNC viscosity, thus advancing comprehension of PNCs behavior in relation to the synthesis parameters. The modeling facilitated precise formulation to predict PNC viscosity with high accuracy, as confirmed by a mean squared error (MSE) of 3.81 and an R2 of 0.993. Moreover, the PNCs demonstrated broad-spectrum antimicrobial activity, reaching an inhibition plateau during the first week, confirming its efficacy as a versatile antibacterial and antifungal agent. Combining advanced data modeling techniques with biological assessments, this integrated approach represents a step forward in understanding and optimizing polymeric nanostructures. [ABSTRACT FROM AUTHOR]

Using existing adrentimicrobials with essential oil components to prevent antimicrobial resistance is an alternative strategy. This study aimed to evaluate the resistance status, synergistic combinations, and in vitro biofilm formation activities of clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), Stenotrophomonas maltophilia and Candida albicans against antimicrobial agents and cinnamaldehyde, carvacrol, eugenol, limonene and eucalyptol. Antimicrobial activities were evaluated by microdilution, cytotoxicity by XTT, synergy by checkerboard and time-kill, and biofilm inhibition by microplate methods. Cinnamaldehyde and carvacrol showed strong antimicrobial activity. Synergistic effects were observed when using all essential oils with antimicrobials. Only two C. albicans isolates showed antagonism with cinnamaldehyde and fluconazole. The constituents showed cytotoxic effects in the L929 cell line (except limonene). A time-kill analysis revealed a bacteriostatic effect on S. maltophilia and MRSA isolates and a fungicidal effect on C. albicans isolates. These results are important for further research to improve antimicrobial efficacy or to develop new agents. [ABSTRACT FROM AUTHOR]

Antimicrobial drug resistance poses a global health threat, requiring a deeper understanding of the evolutionary processes that lead to its emergence in pathogens. Complex evolutionary dynamics involve multiple mutations that can result in cooperative or competitive (clonal interference) effects. Candida albicans, a major fungal pathogen, displays high rates of copy number variation (CNV) and loss of heterozygosity (LOH). CNV and LOH events involve large numbers of genes and could synergize during evolutionary adaptation. Understanding the contributions of CNV and LOH to antifungal drug adaptation is challenging, especially in the context of whole-population genome sequencing. Here, we document the sequential evolution of fluconazole tolerance and then resistance in a C. albicans isolate involving an initial CNV on chromosome 4, followed by an LOH on chromosome R that involves KSR1. Similar LOH events involving KSR1, which encodes a reductase in the sphingolipid biosynthesis pathway, were also detected in independently evolved fluconazole resistant isolates. We dissect the specific KSR1 codons that affect fluconazole resistance and tolerance. The combination of the chromosome 4 CNV and KSR1 LOH results in a >500-fold decrease in azole susceptibility relative to the progenitor, illustrating a compelling example of rapid, yet step-wise, interplay between CNV and LOH in drug resistance evolution. Author summary: The rise of drug-resistant microbes is a global health crisis. To combat this, we need to understand how these organisms evolve drug resistance. This study focuses on Candida albicans, a common fungal pathogen, and its ability to develop resistance to fluconazole, a widely used antifungal drug. We observe C. albicans rapidly evolve drug resistance through a two-step process involving large-scale genetic changes. First, it undergoes a copy number amplification, then it undergoes a loss of heterozygosity at the KSR1 gene, which is involved in sphingolipid biosynthesis. These changes work together to dramatically increase the fungus's ability to survive in the presence of the drug. This research highlights how quickly and efficiently yeast can adapt to overcome antifungal drug and emphasizes the importance of studying large-scale genetic changes, not just individual mutations, when investigating drug resistance. Our findings could help in developing new strategies to predict and prevent the emergence of resistant pathogens, ultimately improving patient care in the face of this growing threat. [ABSTRACT FROM AUTHOR]

Medicinal chemistry highly values the benzimidazole scaffold as a pharmacophore owing to its versatile range of biological functions. In the present study, 17 derivatives of 2‐aryl‐N1‐arylacetamido benzimidazoles 3(a–q) were synthesized by nucleophilic substitution reactions between different 2‐chloro‐N‐(aryl)‐acetamides 2(a–q) and 2‐(4‐chlorophenyl)‐1H‐benzo[d]imidazole (1) in N, N‐dimethylformamide, and evaluated for in vitro anti‐HIV and antifungal activities. Of these derivatives, compounds 3 a, 3 b, 3 i, and 3 n showed moderate inhibitory efficacy against HIV‐1 RT, whereas the remaining compounds showed negligible activity compared to the standard drug efavirenz. In contrast, most of the test compounds demonstrated significant efficacy against fungal strains such as Candida albicans and Aspergillus niger. Compounds 3 a, 3 f, 3 m, and 3 n were the most effective antifungal agents. We applied computational approaches to rationalize the potency of the newly synthesized inhibitors. [ABSTRACT FROM AUTHOR]

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]

Background: cultivated and wild plants are used to treat different ailments. The Astragalus genus is found in temperate and dry climates; thus, it is found in Egypt and the arab world. Astragalus caprinus has a good amount of bioactive chemicals, which may help explain its therapeutic effects in reducing the risk of consequences from disease. Method: The phytochemical investigation of the herb and roots of Astragalus caprinus L. included the analytical characterization for the petroleum ether components by GC/MS, unsaponifiable matter (unsap. fraction), and fatty acids (FAME) investigation by GLC analysis. Main flavonoids were chromatographically isolated from ethyl acetate and n-butanol extracts. In vitro antimicrobial activity has been tested against the Gram-positive bacteria Staphylococcus aureus and Streptococcus mutans for different plant extracts, the Gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumonia, the fungus Candida albicans and Aspergillus niger, and the Escherichia coli bacterium. Metabolite cytotoxicity was examined using the MTT assay against HepG-2 (human liver carcinoma) and MCF-7 (breast carcinoma). Results: Identifying the important components of the herb and root petroleum ether extracts was achieved. Using column chromatography, luteolin, cosmosiin (apigenin-7-O-glucoside), and cynaroside (luteolin-7-O-glucoside) were separated and identified using UV, NMR, and Mass Spectroscopy. Root extracts displayed potential antimicrobial activity against most of the tested pathogens. Both extracts (herb and roots) were active against the MCF-7 cell line and HepG-2 cell line with IC50 62.5 ± 0.64 and 72.4 ± 2.3 µg/ml, and 75.9 ± 2.5 and 96.8 ± 4.2 µg/ml, respectively. Conclusion: Astragalus caprinus seems to be a promising source of bioactive compounds that could potentially aid in preventing disease complications and address common health issues in developing countries. Moreover, the various parts of this plant could be utilized as natural raw materials for producing health-boosting products that could address common health issues in developing countries. [ABSTRACT FROM AUTHOR]

Introduction: Candida species, opportunistic yeast, are the second most common cause of female vulvovaginal candidiasis. This study aimed to evaluate the antifungal susceptibility profile of the isolated Candida species in pregnant women in Hajjah governorate, Yemen. Methods: A hospital-based cross-sectional study was conducted among 396 pregnant women attending Authority AL-Gumhorri Hospital Hajjah between February and July 2023. Vaginal swabs were collected, and Candida species were isolated and identified based on the standard laboratory method. Furthermore, the antifungal drug susceptibility of Candida species was determined by the Kirby-Bauer technique. Results and discussion: The prevalence of vaginal Candida infection among pregnant women was 61.4%. Candida albicans was the most predominant species (59.26%), followed by Candida krusei(13.58%), Candida Tropicalis (11.12%), Candida Grabata (9.87%), and Candida dubliniensis (6.17%). The highest rate of Candida infections was among women aged 24-30 years (71.9%) who finished primary school (77.8%), with the third trimester (80%), multigravida (66.1%), and recurrent infection (67.7%) showing significant differences (P < 0.05). The Candida albicans isolates were resistant to clotrimazole and itraconazole at 34.7% and 23.6%, respectively. In addition, the resistance of Candida krusei, Candida tropicalis, Candida glabrata, and Candida dublinensis isolates to fluconazole, voriconazole, voriconazole, and nystatin was 57.6%, 63%, 43.8%, and 60%, respectively. Additionally, approximately 46.2% of isolated Candida albicans exhibited one kind of antifungal drug resistance, whereas 38.7% of isolated non-albicans exhibited resistance to three different antifungal agents. According to the above findings, Candida infection is highly prevalent in Yemen and quite widespread. Interventions in health education are advised to increase women's knowledge of vaginitis and its prevention. The antifungal susceptibility test may also be helpful in determining the best medication for each patient. [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]

The newly synthesized 1,2,3-triazole-thiazole hybrids were first evaluated for their antimicrobial activity against different microbial strains. Most of it showed a marked selectivity against Gram-positive and Gram-negative bacterial strains. The MIC assay was then assessed; for S. aureus, 4a was equipotent to the reference neomycin, while 3a, 3b, and 8b were 2-fold lower. For E. coli, compounds 3a, 4a, and 8c were equipotent to neomycin, while 5a was 8-fold higher, and 8d was 2-fold higher. Most of tested compounds showed superiority to the reference drug against C. albicans; 8a and 8e showed MIC value of 16-fold higher than neomycin, while 3a was 8-fold higher. Also, 3b and 8f were 4-fold higher; 8d was 2-fold higher, while 5a was equipotent to neomycin against the same microbe. Further biofilm formation inhibition assay was conducted to the most active compounds, 5a was the most active against the three types of bacterial strains. [ABSTRACT FROM AUTHOR]

Invasive fungal infections are rapidly increasing, and the opportunistic pathogenic Candida species are the fourth most common cause of nosocomial systemic infections. The current antifungal classes, of which azoles are the most widely used, all have shortcomings. Azoles are generally considered fungistatic rather than fungicidal, they do not actively kill fungal cells and therefore resistance against azoles can be rapidly acquired. Combination therapies with azoles provide an interesting therapeutic outlook and agents limiting iron are excellent candidates. We summarize how iron is acquired by the host and transported towards both storage and iron‐utilizing organelles. We indicate whether these pathways alter azole susceptibility and/or tolerance, to finally link these transport mechanisms to mitochondrial iron availability. In this review, we highlight putative novel intracellular iron shuffling mechanisms and indicate that mitochondrial iron dynamics in relation to azole treatment and iron limitation is a significant knowledge gap. [ABSTRACT FROM AUTHOR]

(1) Background: The adhesion and microbiological behaviour of thermoplastic PETG dental appliance surfaces is governed by roughness parameters. The aim of this research was to evaluate the antibiofilm activity of alkaline peroxide-based disinfectant in Candida albicans biofilms on thermoplastic PETG, related to artificial ageing and surface characteristics, on multiscale levels. (2) Methods: In the present study, two PETG materials were investigated: Crystal® (Bio Art Dental Equipment, Sao Carlos, Brazil), noted as C, and Duran® (Scheu-Dental GmbH, Iserlohn, Germany)—noted as D. Half of the specimens were thermally cycled (TC), resulting in four sample groups, as follows: C, CTC, D, and DTC. Surface roughness was evaluated on different scale topographies. The biofilms were grown on the surfaces. An alkaline peroxide-based disinfectant was used. Statistical analyses were performed. (3) Results: Related to nanoroughness, there are insignificant differences among materials or related to thermocycling. More irregular surfaces are associated with larger grain sizes. After thermocycling, micro-roughness values increase. Disinfectant activity decreases the amount of biofilm developed on the surfaces, significantly in the two groups, but is not correlated to the material and artificial ageing. (4) Conclusion: The impact of surface roughness (Ra) on biofilm constitution is controlled by different scale topographies. [ABSTRACT FROM AUTHOR]

In this study, a novel oral formulation of berberine hydrochloride (BBH) hydrogel was successfully synthesized through physical cross-linking using chitosan (CS) and carboxymethyl-β-cyclodextrin (CMCD). The characterization results confirmed the successful synthesis of the CS/CMCD hydrogel and the subsequent loading of BBH into this composite (CS/CMCD/BBH) was effectively accomplished. The BBH was used as a model drug and the resulting hydrogel demonstrated a sustained drug release profile. In addition to its improved solubility and sustained release characteristics, the hydrogel exhibited excellent antibacterial activity against common pathogens such as Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Candida albicans (C. albicans). Additionally, in vitro studies indicated that the hydrogel was not cytotoxic to NIH3T3 and HaCaT cells, suggesting its safety for biomedical applications. This lack of cytotoxic effects, combined with the mechanical strength, solubility improvements, and antibacterial properties of the hydrogel, positions the CS/CMCD/BBH hydrogel as a promising candidate for the effective oral delivery of BBH. By addressing the solubility and delivery challenges of BBH, this hydrogel offers a viable solution for the oral administration of BBH, with potential applications in various biomedical fields. [ABSTRACT FROM AUTHOR]

Previous reports have demonstrated that the peptide derived from LfcinB, R-1-R, exhibits anti-Candida activity, which is enhanced when combined with an extract from the Bidens pilosa plant. However, the mechanism of action remains unexplored. In this research, a proteomic study was carried out, followed by a bioinformatic analysis and biological assays in both the SC5314 strain and a fluconazole-resistant isolate of Candida albicans after incubation with R-1-R. The proteomic data revealed that treatment with R-1-R led to the up-regulation of most differentially expressed proteins compared to the controls in both strains. These proteins are primarily involved in membrane and cell wall biosynthesis, membrane transport, oxidative stress response, the mitochondrial respiratory chain, and DNA damage response. Additionally, proteomic analysis of the C. albicans parental strain SC5314 treated with R-1-R combined with an ethanolic extract of B. pilosa was performed. The differentially expressed proteins following this combined treatment were involved in similar functional processes as those treated with the R-1-R peptide alone but were mostly down-regulated (data are available through ProteomeXchange with identifier PXD053558). Biological assays validated the proteomic results, evidencing cell surface damage, reactive oxygen species generation, and decreased mitochondrial membrane potential. These findings provide insights into the complex antifungal mechanisms of the R-1-R peptide and its combination with the B. pilosa extract, potentially informing future studies on natural product derivatives. [ABSTRACT FROM AUTHOR]

Phosphorus is essential in all cells' structural, metabolic and regulatory functions. For fungal cells that import inorganic phosphate (Pi) up a steep concentration gradient, surface Pi transporters are critical capacitators of growth. Fungi must deploy Pi transporters that enable optimal Pi uptake in pH and Pi concentration ranges prevalent in their environments. Single, triple and quadruple mutants were used to characterize the four Pi transporters we identified for the human fungal pathogen Candida albicans, which must adapt to alkaline conditions during invasion of the host bloodstream and deep organs. A high-affinity Pi transporter, Pho84, was most efficient across the widest pH range while another, Pho89, showed high-affinity characteristics only within one pH unit of neutral. Two low-affinity Pi transporters, Pho87 and Fgr2, were active only in acidic conditions. Only Pho84 among the Pi transporters was clearly required in previously identified Pi-related functions including Target of Rapamycin Complex 1 signaling, oxidative stress resistance and hyphal growth. We used in vitro evolution and whole genome sequencing as an unbiased forward genetic approach to probe adaptation to prolonged Pi scarcity of two quadruple mutant lineages lacking all 4 Pi transporters. Lineage-specific genomic changes corresponded to divergent success of the two lineages in fitness recovery during Pi limitation. Initial, large-scale genomic alterations like aneuploidies and loss of heterozygosity eventually resolved, as populations gained small-scale mutations. Severity of some phenotypes linked to Pi starvation, like cell wall stress hypersensitivity, decreased in parallel to evolving populations' fitness recovery in Pi scarcity, while severity of others like membrane stress responses diverged from Pi scarcity fitness. Among preliminary candidate genes for contributors to fitness recovery, those with links to TORC1 were overrepresented. Since Pi homeostasis differs substantially between fungi and humans, adaptive processes to Pi deprivation may harbor small-molecule targets that impact fungal growth, stress resistance and virulence. Author summary: Fungi must be able to access enough phosphate in order to invade the human body. Virulence of Candida albicans, the most common invasive human fungal pathogen, is known to decrease when one of the proteins that brings phosphate into the fungal cell, called Pho84, is disabled. We identified three more proteins in C. albicans that transport phosphate into the cell. We found that Pho84 plays the largest role among them across the broadest range of environmental conditions. After eliminating all 4 of these transporters, we let two resulting mutants evolve for two months in limited phosphate and analyzed the growth and stress resistance of the resulting populations. We analyzed genomes of representative populations and found that early adaptations to phosphate scarcity occurred together with major changes to chromosome configurations. In later stages of the adaptation process, these large-scale changes disappeared as populations gained small-scale mutations that increased cells' ability to grow in limited phosphate. Some but not all of these favorable mutations improved resistance of evolving populations to stressors like membrane- and cell wall stress. Pinpointing distinct mutation combinations that affect stress resistance differently in populations adapting to scarce phosphate, may identify useful antifungal drug targets. [ABSTRACT FROM AUTHOR]

Background: Cymbopogon is a member of the family Poaceae and has been explored for its phytochemicals and bioactivities. Although the antimicrobial activities of Cymbopogon spp. extracts have been extensively studied, comprehensive analyses are required to identify promising compounds for the treatment of antimicrobial resistance. Therefore, this study investigated the antioxidant and antimicrobial properties of Cymbopogon spp. ethanolic extracts in every single organ. Methods: Ethanolic extracts were obtained from three Indonesian commercial species of Cymbopogon spp., namely Cymbopogon citratus (L.) Rendle, Cymbopogon nardus (DC.) Spatf., and Cymbopogon winterianus Jowitt. The leaf, stem, and root extracts were evaluated via metabolite profiling using gas chromatography-mass spectrometry (GC–MS). In silico and in vitro analyses were used to evaluate the antioxidant and antimicrobial properties of the Cymbopogon spp. ethanolic extracts. In addition, bioactivity was measured using cytotoxicity assays. Antioxidant assays were performed using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azino-bis [3-ethylbenzothiazoline-6-sulfonic acid (ABTS) to determine toxicity to Huh7it-1 cells using a tetrazolium bromide (MTT) assay. Finally, the antimicrobial activity of these extracts was evaluated against Candida albicans, Bacillus subtilis, Staphylococcus aureus, and Escherichia coli using a well diffusion assay. Results: GC–MS analysis revealed 53 metabolites. Of these, 2,5-bis(1,1-dimethylethyl)- phenol (27.87%), alpha-cadinol (26.76%), and 1,2-dimethoxy-4-(1-propenyl)-benzene (20.56%) were the predominant compounds. C. winterianus and C. nardus leaves exhibited the highest antioxidant activity against DPPH and ABTS, respectively. Contrastingly, the MTT assay showed low cytotoxicity. C. nardus leaf extract exhibited the highest antimicrobial activity against E. coli and S. aureus, whereas C. winterianus stem extract showed the highest activity against B. substilis. Furthermore, computational pathway analysis predicted that antimicrobial activity mechanisms were related to antioxidant activity. Conclusions: These findings demonstrate that the leaves had strong antioxidant activity, whereas both the leaves and stems showed great antimicrobial activity. Furthermore, all Cymbopogon spp. ethanolic extracts showed low toxicity. These findings provide a foundation for future studies that assess the clinical safety of Cymbopogon spp. as novel drug candidates. [ABSTRACT FROM AUTHOR]

Background: The emergence of tolerance to antifungal agents in Candida albicans complicates the treatment of fungal infections. Understanding the mechanisms underlying this tolerance is crucial for developing effective therapeutic strategies. Objective: This study aims to elucidate the genetic and molecular basis of ketoconazole tolerance in C. albicans, focusing on the roles of chromosomal aneuploidy, Hsp90, and calcineurin. Methods: The wild-type C. albicans strain SC5314 was exposed to increasing concentrations of ketoconazole (0.015-32 µg/mL) to select for tolerant adaptors. Disk diffusion and spot assays were used to assess tolerance. Wholegenome sequencing identified chromosomal changes in the adaptors. The roles of Hsp90 and calcineurin in maintaining and developing ketoconazole tolerance were investigated using specific inhibitors and knockout strains. Results: Adaptors exhibited tolerance to ketoconazole concentrations up to 16 µg/mL, a significant increase from the parent strain's inhibition at 0.015 µg/mL. All tolerant adaptors showed amplification of chromosome R, with 29 adaptors having trisomy and one having tetrasomy. This aneuploidy was unstable, reverting to euploidy and losing tolerance in drug-free conditions. Both Hsp90 and calcineurin were essential for maintaining and developing ketoconazole tolerance. Inhibition of these proteins resulted in loss of tolerance. The efflux gene CDR1 was not required for the development of tolerance. Chromosome R trisomy and tetrasomy induce cross-tolerance to other azole antifungal agents, including clotrimazole and miconazole, but not to other antifungal classes, such as echinocandins and pyrimidines, exemplified by caspofungin and 5-flucytosine. Conclusion: Ketoconazole tolerance in C. albicans is mediated by chromosomal aneuploidy, specifically chromosome R amplification, and requires Hsp90 and calcineurin. These findings highlight potential targets for therapeutic intervention to combat antifungal tolerance and improve treatment outcomes. [ABSTRACT FROM AUTHOR]

Development of resistance and tolerance to antifungal drugs in Candida albicans can compromise treatment of infections caused by this pathogenic yeast species. The uniquely expanded C. albicans TLO gene family is comprised of 14 paralogous genes which encode Med2, a subunit of the multiprotein Mediator complex which is involved in the global control of transcription. This study investigates the acquisition of fluconazole tolerance in a mutant in which the entire TLO gene family has been deleted. This phenotype was reversed to varying degrees upon reintroduction of representative members of the alpha- and beta-TLO clades (i.e. TLO1 and TLO2), but not by TLO11, a gamma-clade representative. Comparative RNA sequencing analysis revealed changes in the expression of genes involved in a range of cellular functions, including ergosterol biosynthesis, mitochondrial function, and redox homeostasis. This was supported by the results of mass spectrometry analysis, which revealed alterations in sterol composition of the mutant cell membrane. Our data suggest that members of the C. albicans TLO gene family are involved in the control of ergosterol biosynthesis and mitochondrial function and may play a role in the responses of C. albicans to azole antifungal agents. [ABSTRACT FROM AUTHOR]

The antibiofilm and antimicrobial properties of tropical honey types including Malaysian stingless bee honey remain explicitly unexplored when compared with Apies honey. The antibiofilm and antimicrobial activities of the Malaysian Trigona honey were characterized with two stinging bee honey types (Centaurea hyalolepis and Citrus honeys) from Jordan. The antibiofilm and antimicrobial investigations were conducted on a set of seven microbial strains; five bacterial species of Pseudomonas aeruginosa ATCC 10145, Streptococcus pyogenes ATCC 19615, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 13883, and two fungal strains Candida albicans ATCC 10231 and Candida krusei ATCC 14243. The antimicrobial investigations revealed a broad spectrum activity for Trigona honey against Gram-positive, Gram-negative, and fungal strains over the two honey types. One-way ANOVA showed a significant difference (p < 0.001) in the zone of inhibition ranging from 9 to 25 mm and minimum inhibition activity (MIC) ranged from 9.4–29.6% (w/v) against the microbial strains. Moreover, the addition of honey to established biofilms has induced a degradation activity in the biofilm mass. Two-way ANOVA showed a significant biofilm degradation proportion (p < 0.001) ranging from 1.3% to 91.3% following treatment with Trigona honey and the other honey types in relevance to the concentration ranging from 10% to 50% (w/v). Moreover, the antibiofilm activity was highly consistent with MIC affecting bacterial growth inhibition. In conclusion, a robust antimicrobial and antibiofilm activity for Trigona stingless bee honey over the stinging bee Centaurea hyalolepis and Citrus honeys is noticed which endows the usage of Trigona honey in the antimicrobial industry. [ABSTRACT FROM AUTHOR]

Background: Although synthetic preservatives and antioxidants may have high antimicrobial and antioxidant activity, they are usually associated with adverse effects on human health. Currently, there is a growing interest in natural antimicrobial and antioxidant agents. This study aimed to evaluate the antimicrobial activity of two medicinal plant extracts and one active compound. Olive leaf extracts (0.2, 0.3, and 0.4% w/v), oleuropein (0.2, 0.4, and 0.6% w/v), thyme oil (0.1%), and oleuropein in combination with thyme oil (0.4% w/v and 0.1% v/v) were used against three bacterial strains (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) and two fungal strains (Candida albicans and Aspergillus niger). Results: The use of oleuropein resulted in complete antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. In this context, a reduction of 7 logs was achieved during the storage period (4 weeks). Oleuropein showed no fungal activity at low concentrations (0.2%), but Aspergillus niger was reduced by 2.35 logs at higher concentrations (0.6% w/v). Similar antibacterial and antifungal properties were observed for the olive leaf extracts. Oleuropein at a concentration of 0.4 w/v and a mixture of oleuropein and thyme at concentrations of 0.4 and 0.1 (v/v) showed strong antimicrobial activity against the studied microorganisms. Conclusion: Olive leaf extract, thyme oil, and oleuropein have strong antibacterial and weak antifungal properties. There was a good synergistic effect between oleuropein and thymol. [ABSTRACT FROM AUTHOR]

N-Furfuryl allylamines react with a broad range of isocyanates, isothiocyanates, isoselenocyanates with the formation of a 3a,6-epoxyisoindole core in one synthetic stage. The interaction sequence involves two consecutive steps: the nucleophilic addition reaction and the intramolecular Diels–Alder furane (IMDAF) reaction. The scope and limitations of the proposed method were thoroughly investigated, and it was revealed that the key [4+2] cycloaddition step proceeds through an exo-transition state, giving rise to the exclusive formation of a single diastereomer of the target heterocycle. Dynamic temperature NMR analysis allowed to fully investigating a case of coalescence of NMR signals and determined the coalescence temperature during the transition O → Se. The antimicrobial properties of the obtained compounds against sensitive strains of yeast Candida albicans, fungus Aspergillus niger and bacteria including Staphylococcus aureus, Micrococcus luteus, Pseudomonas fluorescens were identified. [ABSTRACT FROM AUTHOR]

Candida albicans, an opportunistic oral pathogen, synergizes with Staphylococcus aureus, allowing bacteria to co-invade and systemically disseminate within the host. Studying human-microbe interactions creates the need for a universal culture medium that supports fungal, bacterial, and human cell culturing, while allowing sensitive analytical approaches such as OMICs and chromatography techniques. In this study, we established a fully defined, customizable adaptation of Dulbecco's modified Eagle medium (DMEM), allowing multi-kingdom culturing of S. aureus, C. albicans, and human oral cell lines, whereas minimal version of DMEM (mDMEM) did not support growth of S. aureus, and neither did supplementation with dextrose, MEM non-essential amino acids, pyruvate, and Glutamax. This new medium composition, designated as "mDMEM-DMP," promoted growth of all tested S. aureus strains. Addition of 25 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) further improved growth, while higher concentrations did not improve growth any further. Higher concentrations of HEPES did result in prolonged stabilization of medium pH. mDMEM-DMP promoted (hyphal) C. albicans monoculturing and co-culturing on both solid and semi-solid surfaces. In contrast to S. aureus, addition of HEPES reduced C. albicans maximum culture optical density (OD). Finally, only buffered mDMEM-DMP (100 mM HEPES) was successful in maintaining the metabolic activity of human oral Ca9-22 and HO1N1 cell lines for 24 hours. Altogether, our findings show that mDMEM-DMP is a versatile and potent culture medium for both microbial and human cell culturing, providing a customizable platform to study human as well as microbial molecular physiology and putative interactions. [ABSTRACT FROM AUTHOR]

Root caries is a subtype of dental caries that predominantly impacts older adults. The occurrence and progression of root caries are associated with the homeostasis of dental plaque biofilm, and microbial synergistic and antagonistic interactions in the biofilm play a significant role in maintaining the oral microecological balance. The objective of the current study was to investigate the role of Veillonella parvula in the microbial interactions and the pathogenesis of root caries. The analysis of clinical samples from patients with/without root caries revealed that Veillonella and V. parvula were abundant in the saliva of patients with root caries. More importantly, a significantly increased colonization of V. parvula was observed in root carious lesions. Further in vitro biofilm and animal study showed that V. parvula colonization increased the abundance and virulence of Streptococcus mutans and Candida albicans, leading to the formation of a polymicrobial biofilm with enhanced anti‐stress capacity and cariogenicity, consequently exacerbating the severity of carious lesions. Our results indicate the critical role of V. parvula infection in the occurrence of root caries, providing a new insight for the etiological investigation and prevention of root caries. [ABSTRACT FROM AUTHOR]

To determine the content of phenolcarboxylic acids using gas chromatography–mass spectrometer (GC–MS) in the obtained extract, conduct a study of the antimicrobial, antifungal, and antioxidant activities of Rubus idaeus shoot lipophilic extract. The quantification of phenolcarboxylic was accomplished through GC–MS, antioxidant activity was assessed by potentiometric method, antimicrobial and antifungal activities were determined by well method. The 8 compounds were identified by the GC–MS method. The vanillic acid (2.59 ± 0.08 mg/100 g), benzoic acid (1.51±0.08 mg/100 g), and ferulic acid (0.79±0.04 mg/100 g) dominated in the obtained lipophilic R. idaeus shoot extract. Bacillus subtilis (17.00 ± 0.50 mm) was the most sensitive to lipophilic extract, whereas Proteus vulgaris was the most resistant to the lipophilic extract. Moreover, Candida albicans was medium sensitive to lipophilic extract (13.50 ± 0.50 mm). The antioxidant activity was 1.00 mmol-equiv./mdry res; according to Maslov's antioxidant level classification it has low level. The lipophilic extract from R. idaeus shoots contains various phenolcarboxylic acids, including vanillic acid, benzoic acid, ferulic acid, p-hydroxybenzoic acid, syringic acid, gentisic acid, salicylic acid, and phenylacetic acid, with the highest concentrations observed for vanillic, benzoic, and ferulic acids. This study highlights the antimicrobial and antifungal properties of the R. idaeus shoot lipophilic extract. However, the obtained lipophilic extract showed a relatively low level of antioxidant activity. Consequently, the derivatives of phenolcarboxylic acids play a substantial role in the antimicrobial and antifungal effects, whereas their contribution to antioxidant activity appears to be limited. [ABSTRACT FROM AUTHOR]

Summary: Impacts of aqueous and ethanolic extracts of garlic were investigated in suppressing bacterial growth and biogenic amine (BA) formation by selected foodborne pathogens (Candida albicans, Salmonella paratyphi A, Escherichia coli and Staphylococcus aureus) and fish spoilage bacteria (Enterococcus faecalis, Photobacterium damselae and Pseudomonas luteola). The spread‐plate method was used to monitor bacterial growth in histidine decarboxylase broth (HDB), whereas the rapid high‐performance liquid chromatographic (HPLC) method was used for BA analysis. Bacterial growth and their ammonia and BA production were monitored using HDB. The results showed that bacterial growth on HDB was in the range from 9.13, for P. luteola, to 9.54 log CFU (colony‐forming units) mL−1, for S. aureus and C. albicans. The presence of garlic extracts in HDB resulted considerably in lowering bacterial growth and BA formation (P < 0.05). The highest inhibitory activities of ethanolic and water garlic extracts were obtained for Gram‐positive S. aureus with 1.4 and 1.5 logarithmic reduction on bacterial growth, followed by Gram‐negative Salmonella Paratyphi A and E. coli. Application of garlic extracts, mainly ethanolic ones, showed a significant inhibitory effect on bacterial ammonia production, with 4‐100‐fold lower ammonia accumulation (P < 0.05). Bacteria produced all tested BAs, mainly dopamine, agmatine and tryptamine. The highest levels of histamine and tyramine (61.99 and 36.45 mg L−1) were produced by S. aureus. In the presence of aqueous or ethanolic garlic extracts, putrescine production by E. faecalis was around 110‐fold lower than that of the control group. Results revealed that both garlic extracts are potent antimicrobials that can control the growth of foodborne pathogens and their harmful BA formation. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine, at the phenotypic and molecular levels, resistance and virulence markers in Candida spp. isolated from community-acquired infections in Bucharest outpatients during 2021, and to demonstrate the efficiency of alternative solutions against them based on silver nanoparticles (AgNPs). Methods: A total of 62 Candida spp. strains were isolated from dermatomycoses and identified using chromogenic culture media and MALDI-TOF MS, and then investigated for their antimicrobial resistance and virulence markers (VMs), as well as for metabolic enzymes using enzymatic tests for the expression of soluble virulence factors, their biofilm formation and adherence capacity on HeLa cells, and PCR assays for the detection of virulence markers and the antimicrobial activity of alternative solutions based on AgNPs. Results: Of the total of 62 strains, 45.16% were Candida parapsilosis; 29.03% Candida albicans; 9.67% Candida guilliermondii; 3.22% Candida lusitaniae, Candia pararugosa, and Candida tropicalis; and 1.66% Candida kefyr, Candida famata, Candida haemulonii, and Candida metapsilosis. Aesculin hydrolysis, caseinase, and amylase production were detected in the analyzed strains. The strains exhibited different indices of adherence to HeLa cells and were positive in decreasing frequency order for the LIP1, HWP1, and ALS1,3 genes (C. tropicalis/C. albicans). An inhibitory effect on microbial growth, adherence capacity, and on the production of virulence factors was obtained using AgNPs. Conclusions: The obtained results in C. albicans and Candida non-albicans circulating in Bucharest outpatients were characterized by moderate-to-high potential to produce VMs, necessitating epidemiological surveillance measures to minimize the chances of severe invasive infections. [ABSTRACT FROM AUTHOR]

Candida albicans is an oral mucosal commensal fungus that transforms into an opportunistic pathogen under specific conditions, including immunosuppression. It causes oral and systemic candidiasis, which results in a significant health burden. Furthermore, an alarming rise in antifungal drug resistance in Candida species raises the urgent need for novel drugs and drug targets. C. albicans Dfg5 and Dcw1 are homologous cell wall alpha-1,6-mannosidases with critical functions and represent potential new drug targets. Our past studies have shown that Dfg5 and Dcw1 function in cell wall biogenesis through the cross-linking of glycoproteins into the cell wall, thus playing a key role in cell wall integrity. Additionally, Dfg5 and Dcw1 are required for hyphal morphogenesis. However, the exact functions of Dfg5 and Dcw1 in cell wall integrity, hyphal morphogenesis, and pathogenesis are not known. In this study, we determined the relation of Dfg5 and Dcw1 with Hog1 MAPK, which plays a key role in cell wall integrity via the regulation of chitin synthesis in C. albicans. Additionally, we also determined the effects of dfg5 and dcw1 mutations on the gene expression of transcriptional regulators of hyphal morphogenesis. Furthermore, we determined the effects of dfg5 and dcw1 mutations on pathogenesis in a mouse model of oral candidiasis. Our results demonstrate that dfg5 and dcw1 mutations, as well as a hog1 knockout mutation, result in the dysregulation of chitin synthesis, resulting in a cell separation defect. Heterozygous and conditional mutations in dfg5 and dcw1 resulted in decreased transcriptional levels of cst20, a positive regulator of hyphal morphogenesis. However, dfg5 and dcw1 mutations resulted in increased levels of all the five negative regulators of hyphal morphogenesis—Tup1, Nrg1, Mig1, Rbf1, and Rfg1. Additionally, Tup1 levels were significantly higher than other negative regulators, indicating that Dfg5 and Dcw1 function in hyphal morphogenesis by repressing Tup1. Finally, dfg5 and dcw1 mutations affected the ability of C. albicans to cause oral candidiasis in mice. Thus, the cell wall glycosidases Dfg5 and Dcw1 are required for virulence and pathogenesis and represent novel drug targets. [ABSTRACT FROM AUTHOR]

Gentisic acid (2,5-dihydroxybenzoic acid) is primarily found naturally in plants and has demonstrated a significant range of biological activities; however, its efficacy and safety as a topical application ingredient are not yet well established. Thus, the compound's potential antioxidant and antimicrobial properties were evaluated for efficacy, while the cytotoxicity was evaluated for safety. The antioxidant activity, measured by the DPPH kinetic method, showed an Efficiency Concentration (EC50) of 0.09 with an antioxidant reducing power (ARP) of 11.1. The minimum inhibitory concentration (MIC) against Staphylococcus aureus was 4.15 mg/mL, Escherichia coli was 4.00 mg/mL, Candida albicans was 3.00 mg/mL, and Cutibacterium acnes was 3.60 mg/mL, and the MIC for C. acnes has remained unpublished until now. The substance showed low cytotoxicity by the neutral red uptake (NRU) methodology against HaCat, HDFa, and HepG2 cells at concentrations of up to 10.0, 7.3, and 4.0 mM, respectively, also representing unpublished data. This evidence demonstrates gentisic acid as a promising active substance for skin topical application in the cosmetic or pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Although Candida albicans is the most frequently identified Candida species in clinical settings, a significant number of infections related to the non-albicans Candida (NAC) species, Candida krusei, has been reported. Both species are able to produce biofilms and have been an important resistance-related factor to antimicrobial resistance. In addition, the microbial relationship is common in the human body, contributing to the formation of polymicrobial biofilms. Considering the great number of reports showing the increase in cases of resistance to the available antifungal drugs, the development of new and effective antifungal agents is critical. The inhibitory effect of Organoselenium Compounds (OCs) on the development of Candida albicans and Candida krusei was recently demonstrated, supporting the potential of these compounds as efficient antifungal drugs. In addition, OCs were able to reduce the viability and the development of biofilms, a very important step in colonization and infection caused by fungi. Thus, the objective of this study was to investigate the effect of the Organoselenium Compounds (p-MeOPhSe)2, (PhSe)2, and (p-Cl-PhSe)2 on the development of dual-species biofilms of Candida albicans and Candida krusei produced using either RPMI-1640 or Sabouraud Dextrose Broth (SDB) media. The development of dual-species biofilms was evaluated by the determination of both metabolic activity, using a metabolic assay based on the reduction of XTT (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt) assay and identification of either Candida albicans and Candida krusei on CHROMagar Candida medium. Biofilm formation using RPMI-1640 was inhibited in 90, 55, and 20% by 30 µM (p-MeOPhSe)2, (PhSe)2, and (p-Cl-PhSe)2, respectively. However, biofilms produced using SDB presented an inhibition of 62, 30 and 15% in the presence of 30 µM (p-MeOPhSe)2, (PhSe)2, and (p-Cl-PhSe)2, respectively. The metabolic activity of 24 h biofilms was inhibited by 35, 30 and 20% by 30 µM (p-MeOPhSe)2, (PhSe)2, and (p-Cl-PhSe)2, respectively, with RPMI-1640; however, 24 h biofilms formed using SDB were not modified by the OCs. In addition, a great reduction in the number of CFUs of Candida albicans (93%) in biofilms produced using RPMI-1640 in the presence of 30 µM (p-MeOPhSe)2 was observed. However, biofilms formed using SDB and treated with 30 µM (p-MeOPhSe)2 presented a reduction of 97 and 69% in the number of CFUs of Candida albicans and Candida krusei, respectively. These results demonstrated that Organoselenium Compounds, mainly (p-MeOPhSe)2, are able to decrease the metabolic activity of dual-species biofilms by reducing both Candida albicans and Candida krusei cell number during biofilm formation using either RPMI-1640 or SDB. Taken together, these results demonstrated the potential of the OCs to inhibit the development of dual-species biofilms of Candida albicans and Candida krusei. [ABSTRACT FROM AUTHOR]

Two complexes of cobalt (II) with monobasic bi‐coordinated {2‐((isopropylimino)methyl)phenol} and neutral mono‐coordinated {2‐((pyridin‐3‐ylimino)methyl)phenol} ligands were prepared. The ligands were not separated as solids, and the complexes, respectively, [Co(L1)2] C1 and [Co (HL2)2Cl2] C2, were obtained from solutions containing cobalt (II) chloride, salicylaldehyde, and the respective amine. The crystallographic studies confirmed fourfold coordinated cobalt in complexes C1 and C2 via N2O2 and N2Cl2 donor atoms, respectively. Further, these complexes crystallized in the orthorhombic Pbca (C1) and monoclinic I2/a (C2) space groups. Against two fungi, the complexes (20 mg/mL) in DMSO induced only inhibition zones of 11 and 15 mm diameters in Candida albicans strains, but amphotericin B inhibited this fungus by 21 mm. All complexes (20 mg/mL) in DMSO were tested against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa strains. Complex C1 showed similar inhibition zones each with 12 mm diameter against these bacteria, but C2 gave inhibition zones with 17, 21, 19, and 16 mm diameters closer to those due to ampicillin which inhibited these strains by 26, 21, 25, and 26 mm. The complexes' C1 and C2 cytotoxicity was also evaluated in MCF‐7 cancer and baby hamster kidney normal cells, and they, respectively, gave IC50 values of 29.1 and 18.1 μM in the cancer cells and of 35.5 and 17.5 μM in the normal ones. The reference, doxorubicin, induced cytotoxic effect with IC50 = 9.66 and 36.42 μM on the MCF‐7 and baby hamster kidney cells, respectively. Both complexes and the control offered 100% germination for a drought‐resistive wheat cultivar, but complex C1 offered only 95% wheat germination under drought conditions. For a drought‐sensitive wheat cultivar, the control, complex C1, and complex C2 offered 90%, 85%, and 90% germination under normal irrigation and 95%, 100%, and 95% germination under drought. [ABSTRACT FROM AUTHOR]

Due to the significant pharmacophoric role of 1,4‐naphthoquinone moiety, which is found in numerous biologically active natural products and well‐known chemotherapeutic drugs, including doxorubicin, shikonin, and alkannin, a newly prepared ligand ((E)‐1‐((2‐mercaptophenyl)imino)naphthalen‐2(1H)‐one) can be obtained from the condensation of 2‐aminothiophenol with diketone (1,2‐naphthoquinone) to form Schiff base (HL), which has been characterized using elemental analyses, FT‐IR, 1H‐NMR, and mass spectra. The inner ((La(III), Er(III), and Yb(III)) and outer ((Fe(III), Co(II), and Zn(II)) transitionmetal complexes have been prepared in 1:2 ratio and identified by several spectroscopic instruments. Different characterization tools have been used as elemental analyses, 1H‐NMR, molar conductivity, 13C‐NMR, FT‐IR, thermal decomposition (TG and DTG), UV‐vis, X‐ray diffraction, mass spectrometry, solid reflectance, and magnetic moment. All of them are conjugated to confirm the proposed structures of the metal complexes and are complementary. Also, molecular docking studies for the ligand and its Zn(II) and Yb(III) complexes (using MOE program) have been performed to support the experimental biological activity. Molecular docking studies recommended that (Yb(HL)2)Cl3·6H2O complex is more potent against Aspergillus niger fungus when docked with 1Y43 (aspergilloglutamic peptidase enzyme from A. niger) receptor, while Zn(II) complex recorded the strongest binding energy among the docked compounds against 2W3Z(the crystal structure of a Streptococcus mutans CE4 esterase) and 7AB4 (the crystal structure of the Escherichia coli toxin‐antitoxin system HipBST [HipT S59A]) proteins receptors, respectively. Experimental applications of the free ligand and its metal chelates as antimicrobial and antioxidant activities have been carried out. The former occurred against two fungal species (Aspergillus niger [ATCC:16404] and Candida albicans [ATCC:10231]), two G‐positive bacterial species (S. mutans [ATCC:25175] and Staphylococcus aureus [ATCC:13565]) and two G‐negative bacterial species (Klebsiella pneumonia [ATCC:10031] and E. coli [ATCC:10536]). The DPPH scavenging method has been used to measure the antioxidant activity of the tested compounds. [ABSTRACT FROM AUTHOR]

Objective: In this work, in order to optimize the structure of histidine-containing antifungal peptides with a "linear" type of amphipathicity (LTA), we carried out the synthesis and comparative screening of the antifungal activity of a series of histidine-containing SAMPs (F2H7, F2H10, F2H13, F2H16, H10, H10F2) with a "linear" type of amphipathicity that we constructed de novo. We also aimed to study their hemolytic properties, to assess their therapeutic index, and to compare the obtained results with similar data for the antifungal histidine-rich 12-mer peptide P113 (AKRHHGYKRKFH), a drug candidate known as PAC-113, one of the shortest and most active analogues of the natural antifungal histidine-rich peptide Hst 5. Methods: Peptides were synthesized by a solid phase method using a Fmoc-based strategy. To determine the antifungal activity of the peptides, we used the opportunistic fungus strain Candida albicans EMTK 34. The number of microorganisms (titer) in the suspension was determined by optical density at a wavelength of 595 nm. To determine the antifungal activity of the peptides, cell cultures were co-incubated with the studied peptides in 96-well plates. The cells were incubated with the drug for 24 h at 37°C. To assess the antifungal activity of the studied peptides, their minimum inhibitory concentrations (MIC50) were determined, i.e. such peptide concentration at which the growth of microorganisms was suppressed by 50%. To assess the toxicity of the peptides, their hemolytic activity was determined, which was tested against fresh human erythrocytes using a photometric method. To assess the selectivity of the action of peptides, the values of the minimum hemolytic concentration (MHC) of the peptides were determined and the values of their therapeutic index (TI) were calculated as the ratio of the minimum hemolytic concentration (MHC) to the MIC50 value. Results and Discussion: It was shown that the antifungal activity of the studied SAMPLTA increases with an increase in the number of histidine residues in their composition, reaching the maximum value for the histidine-containing peptide F2H16 (MIC50 = 1.0 µM). It has been shown that as the chain length of peptides increases, their hemolytic toxicity also increases. The TI values for these peptides were 233, 247, 79, and 60, respectively. It has been shown that, against C. albicans, histidine-containing SAMP-LTA derivatives with phenylalanine residues at the N-terminus of the peptide (F2H10) are less effective compared to similar peptides (H10F2) containing phenylalanine residues at the C-terminus. Among the studied peptides, the most active was the H10 peptide (MIC50 = 0.7 µM), which does not contain phenylalanine residues, which in its antifungal activity is not only more effective than all other histidine-containing peptides, including the F2H16 peptide with 16 histidine residues, but also 4– 5 times more effective than the antifungal peptide P113 (MIC50 = 3.4 µM), a short active fragment of natural Hst 5, well known from the literature. Among all the studied peptides, H10 and P113 have minimal (almost zero) values of hemolytic activity. However, due to its higher antifungal activity, the selectivity of the H10 peptide (TI > 1400) exceeds the selectivity of the P113 peptide (TI > 340) by more than 4 times. Conclusions: Thus, peptide H10, due to its high antifungal activity, low hemolytic toxicity and, accordingly, high therapeutic significance, can be used as a promising antifungal peptide drug. [ABSTRACT FROM AUTHOR]

The secreted aspartic peptidases (Saps) of Candida albicans play crucial roles in various steps of fungal–host interactions. Using a flow cytometry approach, this study investigated the expression of Saps1–3 antigens after (i) incubation with soluble proteins, (ii) interaction with mammalian cells, and (iii) infection in immunosuppressed BALB/c mice. Supplementation strategies involving increasing concentrations of bovine serum albumin (BSA) added to yeast carbon base (YCB) medium as the sole nitrogenous source revealed a positive and significant correlation between BSA concentration and both the growth rate and the percentage of fluorescent cells (%FC) labeled with anti-Saps1–3 antibodies. Supplementing the YCB medium with various soluble proteins significantly modulated the expression of Saps1–3 antigens in C. albicans. Specifically, immunoglobulin G, gelatin, and total bovine/human sera significantly reduced the %FC, while laminin, human serum albumin, fibrinogen, hemoglobin, and mucin considerably increased the %FC compared to BSA. Furthermore, co-cultivating C. albicans yeasts with either live epithelial or macrophage cells induced the expression of Saps1–3 antigens in 78% (mean fluorescence intensity [MFI] = 152.1) and 82.7% (MFI = 178.2) of the yeast cells, respectively, compared to BSA, which resulted in 29.3% fluorescent cells (MFI = 50.9). Lastly, the yeasts recovered from the kidneys of infected immunosuppressed mice demonstrated a 4.8-fold increase in the production of Saps1–3 antigens (MFI = 246.6) compared to BSA, with 95.5% of yeasts labeled with anti-Saps1–3 antibodies. Altogether, these results demonstrated the positive modulation of Saps' expression in C. albicans by various key host proteinaceous components, as well as by in vitro and in vivo host challenges. [ABSTRACT FROM AUTHOR]