Fungal Pathogen Candida Albicans Research Articles

The spliceosome impacts morphogenesis in the human fungal pathogen Candida albicans.

At human body temperature, the fungal pathogen Candida albicans can transition from yeast to filamentous morphologies in response to host-relevant cues. Additionally, elevated temperatures encountered during febrile episodes can independently induce C. albicans filamentation. However, the underlying genetic pathways governing this developmental transition in response to elevated temperatures remain largely unexplored. Here, we conducted a functional genomic screen to unravel the genetic mechanisms orchestrating C. albicans filamentation specifically in response to elevated temperature, implicating 45% of genes associated with the spliceosome or pre-mRNA splicing in this process. Employing RNA-Seq to elucidate the relationship between mRNA splicing and filamentation, we identified greater levels of intron retention in filaments compared to yeast, which correlated with reduced expression of the affected genes. Intriguingly, homozygous deletion of a gene encoding a spliceosome component important for filamentation (PRP19) caused even greater levels of intron retention compared with wild type and displayed globally dysregulated gene expression. This suggests that intron retention is a mechanism for fine-tuning gene expression during filamentation, with perturbations of the spliceosome exacerbating this process and blocking filamentation. Overall, this study unveils a novel biological process governing C. albicans filamentation, providing new insights into the complex regulation of this key virulence trait.IMPORTANCEFungal pathogens such as Candida albicans can cause serious infections with high mortality rates in immunocompromised individuals. When C. albicans is grown at temperatures encountered during human febrile episodes, yeast cells undergo a transition to filamentous cells, and this process is key to its virulence. Here, we expanded our understanding of how C. albicans undergoes filamentation in response to elevated temperature and identified many genes involved in mRNA splicing that positively regulate filamentation. Through transcriptome analyses, we found that intron retention is a mechanism for fine-tuning gene expression in filaments, and perturbation of the spliceosome exacerbates intron retention and alters gene expression substantially, causing a block in filamentation. This work adds to the growing body of knowledge on the role of introns in fungi and provides new insights into the cellular processes that regulate a key virulence trait in C. albicans.

Strain variation in the Candida albicans iron limitation response.

Iron acquisition is critical for pathogens to proliferate during invasive infection, and the human fungal pathogen Candida albicans is no exception. The iron regulatory network, established in reference strain SC5314 and derivatives, includes the central player Sef1, a transcription factor that activates iron acquisition genes in response to iron limitation. Here, we explored potential variation in this network among five diverse C. albicans strains through mutant analysis, Nanostring gene expression profiling, and, for two strains, RNA-Seq. Our findings highlight four features that may inform future studies of natural variation and iron acquisition in this species. (i) Conformity: In all strains, major iron acquisition genes are upregulated during iron limitation, and a sef1Δ/Δ mutation impairs that response and growth during iron limitation. (ii) Response variation: Some aspects of the iron limitation response vary among strains, notably the activation of hypha-associated genes. As this gene set is tied to tissue damage and virulence, variation may impact the progression of infection. (iii) Genotype-phenotype variation: The impact of a sef1Δ/Δ mutation on cell wall integrity varies, and for the two strains examined the phenotype correlated with sef1Δ/Δ impact on several cell wall integrity genes. (iv) Phenotype discovery: DNA repair genes were induced modestly by iron limitation in sef1Δ/Δ mutants, with fold changes we would usually ignore. However, the response occurred in both strains tested and was reminiscent of a much stronger response described in Cryptococcus neoformans, a suggestion that it may have biological meaning. In fact, we observed that the iron limitation of a sef1Δ/Δ mutant caused recessive phenotypes to emerge at two heterozygous loci. Overall, our results show that a network that is critical for pathogen proliferation presents variation outside of its core functions.IMPORTANCEA key virulence factor of Candida albicans is the ability to maintain iron homeostasis in the host where iron is scarce. We focused on a central iron regulator, SEF1. We found that iron regulator Sef1 is required for growth, cell wall integrity, and genome integrity during iron limitation. The novel aspect of this work is the characterization of strain variation in a circuit that is required for survival in the host and the connection of iron acquisition to genome integrity in C. albicans.

Investigating the synergistic effects of apple vinegar and deep eutectic solvent as natural antibiotics: an experimental and COSMO-RS analysis

ABSTRACT The present investigation examines the antimicrobial and antifungal characteristics of natural deep eutectic solvents (NADES) and apple vinegar in relation to a diverse array of bacterial and fungal strains. The clinical bacterial strains, including gram-negative and gram-positive, and the fungal pathogen Candida albicans, were subjected to solid medium diffusion to determine the inhibitory effects of these compounds. The results show that NADES has superior antimicrobial and antifungal action compared to apple vinegar. The observed inhibitory zones for apple vinegar and NADES varied in length from 16.5 to 24.2 and 16 to 52.5 mm, respectively. The results obtained indicate that no synergy is observed for this mixture (50% AV + 50% NADES). The range of values for bactericidal concentrations (MBC) and minimal inhibitory concentrations (MIC) was 0.0125 to 0.2 and 0.0125 to 0.4 µl/ml, respectively. Antibacterial and antifungal chemicals may be found in apple vinegar and NADES, with NADES offering environmentally safe substitutes for traditional antibiotics. Additional investigation is suggested to refine these compounds for a wide range of bacteria, which could create antimicrobial solutions that are both highly effective and specifically targeted, thereby offering extensive potential in medicine and the environment.

Oral Microbiota Alterations in Subjects with SARS-CoV-2 Displaying Prevalence of the Opportunistic Fungal Pathogen Candida albicans

The oral cavity remains an underappreciated site for SARS-CoV-2 infection despite the myriad of oral conditions in COVID-19 patients. Recently, SARS-CoV-2 was shown to replicate in the salivary gland cells causing tissue inflammation. Given the established association between inflammation and microbiome disruption, we comparatively profiled oral microbial differences at a metagenomic level in a cohort of hospitalized COVID-19 patients and matched healthy controls. Specifically, we aimed to evaluate colonization by the opportunistic fungal pathogen Candida albicans, the etiologic agent of oral candidiasis. Comprehensive shotgun metagenomic analysis indicated that, overall, COVID-19 patients exhibited significantly reduced bacterial and viral diversity/richness; we identified 12 differentially abundant bacterial species to be negatively associated with COVID-19, and the functional pathways of certain bacteria to be highly associated with COVID-19 status. Strikingly, C. albicans was recovered from approximately half of the COVID-19 subjects but not from any of the healthy controls. The prevalence of Candida is likely linked to immune hypo-dysregulation caused by COVID-19 favoring Candida proliferation, warranting investigations into the interplay between Candida and SARS-CoV2 and potential therapeutic approaches directed toward oral candidiasis. Collectively, our findings prompt a reassessment of oral opportunistic infection risks during COVID-19 disease and their potential long-term impacts on oral health.

Sur7 mediates a novel pathway for PI4,5P2 regulation in C. albicans that promotes stress resistance and cell wall morphogenesis.

The human fungal pathogen Candida albicans can cause lethal systemic infections due to its ability to resist stress from the host and to undergo invasive hyphal growth. Previous studies showed that plasma membrane MCC/eisosome domains were important for virulence by promoting the ability of Sur7 to mediate normal cell wall morphogenesis and stress resistance. The sur7Δ mutant displayed abnormal clusters of PI4,5P2, suggesting that misregulation of this lipid underlies the sur7Δ phenotype. To test this, we increased PI4,5P2 levels by deleting combinations of the three PI4,5P2 5' phosphatase genes (INP51, INP52, and INP54) and found that some combinations, such as inp51Δ inp52Δ, gave phenotypes similar the sur7Δ mutant. In contrast, deleting one copy of MSS4, the gene that encodes the 5' kinase needed to create PI4,5P2, reduced the abnormal PI4,5P2 clusters and also decreased the abnormal cell wall and stress sensitive phenotypes of the sur7Δ mutant. Additional studies support a model that the abnormal PI4,5P2 patches recruit septin proteins, which in turn promote aberrant cell wall growth. These results identify Sur7 as a novel regulator of PI4,5P2 and highlight the critical role of PI4,5P2 in the regulation of C. albicans virulence properties.

DNA Damage Checkpoints Govern Global Gene Transcription and Exhibit Species-Specific Regulation on HOF1 in Candida albicans.

DNA damage checkpoints are essential for coordinating cell cycle arrest and gene transcription during DNA damage response. Exploring the targets of checkpoint kinases in Saccharomyces cerevisiae and other fungi has expanded our comprehension of the downstream pathways involved in DNA damage response. While the function of checkpoint kinases, specifically Rad53, is well documented in the fungal pathogen Candida albicans, their targets remain poorly understood. In this study, we explored the impact of deleting RAD53 on the global transcription profiles and observed alterations in genes associated with ribosome biogenesis, DNA replication, and cell cycle. However, the deletion of RAD53 only affected a limited number of known DNA damage-responsive genes, including MRV6 and HMX1. Unlike S. cerevisiae, the downregulation of HOF1 transcription in C. albicans under the influence of Methyl Methanesulfonate (MMS) did not depend on Dun1 but still relied on Rad53 and Rad9. In addition, the transcription factor Mcm1 was identified as a regulator of HOF1 transcription, with evidence of dynamic binding to its promoter region; however, this dynamic binding was interrupted following the deletion of RAD53. Furthermore, Rad53 was observed to directly interact with the promoter region of HOF1, thus suggesting a potential role in governing its transcription. Overall, checkpoints regulate global gene transcription in C. albicans and show species-specific regulation on HOF1; these discoveries improve our understanding of the signaling pathway related to checkpoints in this pathogen.

Biofilm-associated metabolism via ERG251 in Candida albicans.

Biofilm formation by the fungal pathogen Candida albicans is the basis for its ability to infect medical devices. The metabolic gene ERG251 has been identified as a target of biofilm transcriptional regulator Efg1, and here we report that ERG251 is required for biofilm formation but not conventional free-living planktonic growth. An erg251Δ/Δ mutation impairs biofilm formation in vitro and in an in vivo catheter infection model. In both in vitro and in vivo biofilm contexts, cell number is reduced and hyphal length is limited. To determine whether the mutant defect is in growth or some other aspect of biofilm development, we examined planktonic cell features in a biofilm-like environment, which was approximated with sealed unshaken cultures. Under those conditions, the erg251Δ/Δ mutation causes defects in growth and hyphal extension. Overexpression in the erg251Δ/Δ mutant of the paralog ERG25, which is normally expressed more weakly than ERG251, partially improves biofilm formation and biofilm hyphal content, as well as growth and hyphal extension in a biofilm-like environment. GC-MS analysis shows that the erg251Δ/Δ mutation causes a defect in ergosterol accumulation when cells are cultivated under biofilm-like conditions, but not under conventional planktonic conditions. Overexpression of ERG25 in the erg251Δ/Δ mutant causes some increase in ergosterol levels. Finally, the hypersensitivity of efg1Δ/Δ mutants to the ergosterol inhibitor fluconazole is reversed by ERG251 overexpression, arguing that reduced ERG251 expression contributes to this efg1Δ/Δ phenotype. Our results indicate that ERG251 is required for biofilm formation because its high expression levels are necessary for ergosterol synthesis in a biofilm-like environment.

Sequential Induction of Drug Resistance and Characterization of an Initial Candida albicans Drug-Sensitive Isolate.

The pathogenic fungus Candida albicans is a leading agent of death in immunocompromised individuals with a growing trend of antifungal resistance. The purpose is to induce resistance to drugs in a sensitive C. albicans strain followed by whole-genome sequencing to determine mechanisms of resistance. Strains will be assayed for pathogenicity attributes such as ergosterol and chitin content, growth rate, virulence, and biofilm formation. We observed sequential increases in ergosterol and chitin content in fluconazole-resistant isolates by 78% and 44%. Surface thickening prevents the entry of the drug, resulting in resistance. Resistance imposed a fitness trade-off that led to reduced growth rates, biofilm formation, and virulence in our isolates. Sequencing revealed mutations in genes involved in resistance and pathogenicity such as ERG11, CHS3, GSC2, CDR2, CRZ2, and MSH2. We observed an increase in the number of mutations in key genes with a sequential increase in drug-selective pressures as the organism increased its odds of adapting to inhospitable environments. In ALS4, we observed two mutations in the susceptible strain and five mutations in the resistant strain. This is the first study to induce resistance followed by genotypic and phenotypic analysis of isolates to determine mechanisms of drug resistance.

Isotope labeled 3D-Raman confocal imaging and atomic force microscopy study on epithelial cells interacting with the fungus Candida albicans

The human pathogenic fungus Candida albicans damages epithelial cells during superficial infections. Here we use three-dimensional-sequential-confocal Raman spectroscopic imaging and atomic force microscopy to investigate the interaction of C. albicans wild type cells, the secreted C. albicans peptide toxin candidalysin and mutant cells lacking candidalysin with epithelial cells. The candidalysin is responsible for epithelial cell damage and exhibits in its deuterated form an identifiable Raman signal in a frequency region distinct from the cellular frequency region. Vibration modes at 2100–2200 cm−1 attributed to carbon‑deuterium bending and at 477 cm−1, attributed to the nitrogen‑deuterium out-of-plane bending, found around the nucleus, can be assigned to deuterated candidalysin. Atomic force microscopy visualized 100 nm deep lesions on the cell and force-distance curves indicate the higher adhesion on pore surrounding after incubation with candidalysin. Candidalysin targets the plasma membrane, but is also found inside of the cytosol of epithelial cells during C. albicans infection.

Antimicrobial properties of Clausena anisata (Rutaceae) essential oil from Bafou area against the pathogenic fungus Candida albicans and antioxidant activity

The aim of the present work was to determine the antimicrobial and antioxidant activities of Clausena anisata essential oil. The extraction of essential oils was performed by the hydro distillation method with a Clevenger apparatus. The determination of essential oils chemical composition was conducted by gas chromatography and gas chromatography coupled with mass spectrometry. Then the antimicrobial activity was assessed using disk diffusion method and micro titration. In order to determine the antioxidant activity 2 methods were carried out: the free radical scavenging assay was performed using the DPPH+ radical (2,2-diphenyl-1-picrylhydrazyl) and the method with ABTS radical reagents (acid2, 2'-azynobis-[3-ethylbenzothiazoline-6 ​​sulfonic acid]). The yield of extraction of the essential oil was 0.77%. The study of its chemical composition revealed E- anethol (70.77%), methyl iso eugenol (13.85) as major compounds. The anti-radical DPPH test revealed a SC50 of 1g/L; 0.265g/L respectively for DPPH and ABTS tests. The results also highlighted a potent antimicrobial property. An antimicrobial screening study revealed a susceptibility of Candida albicans isolates at a concentration of 8000 ppm. This activity was characterized by minimum inhibitory concentrations of 2000 ppm for all the tested pathogenic yeasts Sab1, Sab2, Sab3, Sab250, Sab2501, Sab256, Sab259 and Sab290. The essential oil minimum inhibitory concentration (MIC) was lower than the MIC of fluconazole. The same observations were resulted with the fungicidal effect. These data can be used as a starting point for subsequent studies to produce antifungal and antioxidant drugs to face the challenge of the antimicrobial resistance and oxidative stress.

Impact of Nitric Oxide-Release Kinetics on Antifungal Activity.

Pathogenic fungi are an increasing health threat due to the rise in drug resistance. The limited number of antifungals currently available and growing incidence of multi-drug-resistant fungi has caused rising healthcare costs and a decreased quality of life for patients with fungal infections. Nitric oxide (NO) has previously been shown to act as an antimicrobial agent, albeit with a limited understanding of the effects of the NO-release kinetics against pathogenic fungi. Herein, the antifungal effects of four nitric oxide-releasing small molecules were studied against the pathogenic fungi Candida albicans, Candida auris, Cryptococcus neoformans, and Aspergillus fumigatus, to demonstrate the broad-spectrum antifungal activity of NO. A bolus dose of NO was found to eradicate fungi after 24 h, where nitric oxide donors with shorter half-lives achieved antifungal activity at lower concentrations and thus had wider selectivity indexes. Each NO donor was found to cause a severe surface destruction of fungi, and all NO donors exhibited compatibility with currently prescribed antifungals against several different fungi species.

Phage-antibiotic combinations to control Pseudomonas aeruginosa–Candida two-species biofilms

Phage-antibiotic combinations to treat bacterial infections are gaining increased attention due to the synergistic effects often observed when applying both components together. Most studies however focus on a single pathogen, although in many clinical cases multiple species are present at the site of infection. The aim of this study was to investigate the anti-biofilm activity of phage-antibiotic/antifungal combinations on single- and dual-species biofilms formed by P. aeruginosa and the fungal pathogen Candida albicans. The Pseudomonas phage Motto in combination with ciprofloxacin had significant anti-biofilm activity. We then compared biofilms formed by P. aeruginosa alone with the dual-species biofilms formed by bacteria and C. albicans. Here, we found that the phage together with the antifungal fluconazole was active against 6-h-old dual-species biofilms but showed only negligible activity against 24-h-old biofilms. This study lays the first foundation for potential therapeutic approaches to treat co-infections caused by bacteria and fungi using phage-antibiotic combinations.

Multifactorial inhibition of Candida albicans by combinations of lactobacilli and probiotic Saccharomyces cerevisiae CNCM I-3856

Strategies against the opportunistic fungal pathogen Candida albicans based on probiotic microorganisms represent a promising alternative to traditional antifungals. Here, we investigated the effects of Lactobacillaceae isolates from fermented foods or the human vagina, alone or in combination with the probiotic yeast Saccharomyces cerevisiae CNCM I-3856, against C. albicans in vitro. Nine out of nineteen tested strains of Lactobacillaceae inhibited growth of C. albicans with inhibition zones of 1–3 mm in spot assays. Five out of nineteen lactobacilli tested as such or in combination with S. cerevisiae CNCM I-3856 also significantly inhibited C. albicans hyphae formation, including Limosilactobacillus fermentum LS4 and L. fermentum LS5 resulting in respectively 62% and 78% hyphae inhibition compared to the control. Thirteen of the tested nineteen lactobacilli aggregated with the yeast form of C. albicans, with Lactiplantibacillus carotarum AMBF275 showing the strongest aggregation. The aggregation was enhanced when lactobacilli were combined with S. cerevisiae CNCM I-3856. No significant antagonistic effects were observed between the tested lactobacilli and S. cerevisiae CNCM I-3856. The multifactorial activity of Lactobacillaceae strains alone or combined with the probiotic S. cerevisiae CNCM I-3856 against C. albicans without antagonistic effects between the beneficial strains, paves the way for developing consortium probiotics for in vivo applications.

Lethal metabolism of Candida albicans respiratory mutants.

The destructive impact of fungi in agriculture and animal and human health, coincident with increases in antifungal resistance, underscores the need for new and alternative drug targets to counteract these trends. Cellular metabolism relies on many intermediates with intrinsic toxicity and promiscuous enzymatic activity generates others. Fuller knowledge of these toxic entities and their generation may offer opportunities of antifungal development. From this perspective our observation of media-conditional lethal metabolism in respiratory mutants of the opportunistic fungal pathogen Candida albicans was of interest. C. albicans mutants defective in NADH:ubiquinone oxidoreductase (Complex I of the electron transport chain) exhibit normal growth in synthetic complete medium. In YPD medium, however, the mutants grow normally until early stationary phase whereupon a dramatic loss of viability occurs. Upwards of 90% of cells die over the subsequent four to six hours with a loss of membrane integrity. The extent of cell death was proportional to the amount of BactoPeptone, and to a lesser extent, the amount of yeast extract. YPD medium conditioned by growth of the mutant was toxic to wild-type cells indicating mutant metabolism established a toxic milieu in the media. Conditioned media contained a volatile component that contributed to toxicity, but only in the presence of a component of BactoPeptone. Fractionation experiments revealed purine nucleosides or bases as the synergistic component. GC-mass spectrometry analysis revealed acetal (1,1-diethoxyethane) as the active volatile. This previously unreported and lethal synergistic interaction of acetal and purines suggests a hitherto unrecognized toxic metabolism potentially exploitable in the search for antifungal targets.

In vitro immune analysis of serum from the hemolymph of the anomuran crab Albunea symmysta (Linnaeus, 1758) displayed diversified reactions

The present investigation aims to substantiate that serum from the hemolymph of anomuran crab Albunea symmysta encompasses multiple immunological reactions in in vitro condition. The serum highly agglutinated human O erythrocytes in the presence of Ba2+. Distinct and unique sugar binding capacity of serum towards laminarin, N-acetyl sugars and higher binding specificity towards a glycoprotein, fetuin was inferred. In vitro enhancement of melanin synthesis due to enhanced oxidation of 3, 4-dihydroxy-dl-phenylalanine (dl-DOPA) by preincubation of nonself molecules with serum phenoloxidase (PO) was documented. Similarly, dl-DOPA oxidation by serum PO was reduced when preincubated with chemical inhibitors and copper chelators. Further, the crab serum lysed the vertebrate erythrocytes with maximum hemolysis against chicken and it unveiled dependency on divalent cation, serum concentration, ionic strength, pH, temperature and time interval. Occurrence of maximum hemolysis at a concentration of 30 µl, pH 8.0, temperature 37 °C and time interval of 60 min in the presence of Ba2+ were documented. Interestingly, serum hemolysis was reduced by different osmoprotectants suggesting a colloid-osmotic mechanism involving in hemolysis. It was observed that A. symmysta serum had antimicrobial activity against Gram-positive Staphylococcus aureus and fungal pathogen Candida albicans. The serum showed higher glycan content, potent lysozyme and free radical scavenging activity suggesting the existence of potential immune molecules of therapeutic use. These results clearly demonstrated the diversified immunogenicity of A. symmysta serum confirming a highly conserved non-specific immunity of crustaceans

A multi-colour fluorogenic tag and its application in Candida albicans.

Fluorescent proteins (FPs) have always been a crucial part of molecular research in life sciences, including the research into the human fungal pathogen Candida albicans, but have obvious shortcomings such as their relatively large size and long maturation time. However, the next generation of FPs overcome these issues and rely on the binding of a fluorogen for the protein to become fluorescently active. This generation of FPs includes the improved version of Fluorescence activating and Absorption Shifting Tag (iFAST). The binding between the fluorogen and the iFAST protein is reversible, thus resulting in reversible fluorescence. The fluorogens of iFAST are analogues of 4-hydroxylbenzylidene-rhodanine (HBR). These HBR analogues differ in spectral properties depending on functional group substitutions, which gives the iFAST system flexibility in terms of absorbance and emission maxima. In this work we describe and illustrate the application of iFAST as a protein tag and its reversible multi-colour characteristics in C. albicans.

One in, one out: Commensal fungus protects against infection.

Gut-resident fungi have a broad influence over health and disease. In this issue of JEM, Sekeresova Kralova et al. (https://doi.org/10.1084/jem.20231686) identify a commensal yeast that displaced fungal pathogen Candida albicans and protected against subsequent invasive infections that originate from the gut.

Oral Rinses: Some Kill and Some Cripple Candida albicans

Introduction: Oral healthcare professionals play a crucial role in guiding patients toward evidence-based choices among the many available oral rinses. In this study, we explored how specific oral rinse formulations affect the viability and modulate critical virulence traits of the opportunistic fungal pathogen Candida albicans. Materials and Methods: We assessed the effects of these oral rinses on the production of germ tube, production of phospholipase and hemolysin, as well as biofilm formation. Results: We found that oral rinses containing cetylpyridinium chloride (CPC) and chlorhexidine (CHX) showed the greatest fungicidal activity with the lowest minimum fungicidal concentrations (0.38% and 0.78%, respectively). Oral rinses based on zinc chloride and sodium fluoride with Miswak bark extract (MIS) or essential oils (EO) had much lower fungicidal activity (8–16 times lower) compared to CHX and CPC. However, they had a significantly greater impact on the virulence traits of C. albicans. They reduced germ tube production by 86–89% (vs. 42% for CHX and 29% for CPC), completely inhibited phospholipase and hemolysin production, and together with the CPC-based oral rinse, exerted the greatest reductions in biofilm formation across all tested concentrations. This was in contrast to both the controls and CHX, which had a minimal effect on biofilm formation. Conclusion: By inhibiting the virulence factors, the oral rinse can have a crippling effect on C. albicans, weakening this opportunistic pathogen and hindering its potential to cause infection.

A Comparative Study of the Antifungal Activity of Fresh and Dried Solanum anguivi Fruits on Candida albicans and Trichophyton rubrum

In Côte d'Ivoire, as elsewhere in Africa, Solanum anguivi Lam is widely used in traditional medicine to treat bacterial and fungal infections. Given the importance of this plant, the extracts 70%, 80% and 100% from fresh and dried fruits was evaluated for the in vitro growth of two isolates of pathogenic fungi (Candida albicans and Trichophyton rubrum), as well as its anti-free radical activity. 
 Antifungal tests were carried out by plating 1000 cells of each isolate on Sabouraud agar medium using the double dilution method in inclined tubes. Both extracts were active on the different strains tested, according to a dose-response relationship based on the principle of the method used.
 However, extracts from fresh fruit showed good activity on C. albicans, while the dried fresh fruit extracts were highly active on T. rubrum.

Candida albicans translocation through the intestinal epithelial barrier is promoted by fungal zinc acquisition and limited by NFκB-mediated barrier protection.

The opportunistic fungal pathogen Candida albicans thrives on human mucosal surfaces as a harmless commensal, but frequently causes infections under certain predisposing conditions. Translocation across the intestinal barrier into the bloodstream by intestine-colonizing C. albicans cells serves as the main source of disseminated candidiasis. However, the host and microbial mechanisms behind this process remain unclear. In this study we identified fungal and host factors specifically involved in infection of intestinal epithelial cells (IECs) using dual-RNA sequencing. Our data suggest that host-cell damage mediated by the peptide toxin candidalysin-encoding gene ECE1 facilitates fungal zinc acquisition. This in turn is crucial for the full virulence potential of C. albicans during infection. IECs in turn exhibit a filamentation- and damage-specific response to C. albicans infection, including NFκB, MAPK, and TNF signaling. NFκB activation by IECs limits candidalysin-mediated host-cell damage and mediates maintenance of the intestinal barrier and cell-cell junctions to further restrict fungal translocation. This is the first study to show that candidalysin-mediated damage is necessary for C. albicans nutrient acquisition during infection and to explain how IECs counteract damage and limit fungal translocation via NFκB-mediated maintenance of the intestinal barrier.