Candida auris Outbreaks: Current Status and Future Perspectives

Microorganisms, Journal Year: 2024, Volume and Issue: 12(5), P. 927 - 927

Published: May 1, 2024

Candida auris has been identified by the World Health Organization (WHO) as a critical priority pathogen on its latest list of fungi. C. infections are reported in bloodstream and less commonly cerebrospinal fluid abdomen, with mortality rates that range between 30% 72%. However, no large-scale epidemiology studies have until now. The diagnosis can be challenging, particularly when employing conventional techniques. This impede early detection outbreaks implementation appropriate control measures. yeast easily spread patients healthcare settings through contaminated environments or equipment, where it survive for extended periods. Therefore, would desirable to screen colonisation. allow facilities identify disease take prevention It is frequently unsusceptible drugs, varying patterns resistance observed among clades geographical regions. review provides updates auris, including epidemiology, clinical characteristics, genomic analysis, evolution, colonisation, infection, identification, profiles, therapeutic options, prevention, control.

Language: Английский

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Treatment of Invasive Aspergillosis: How It’s Going, Where It’s Heading

Mycopathologia, Journal Year: 2023, Volume and Issue: 188(5), P. 667 - 681

Published: April 26, 2023

Abstract Despite improvements in treatment and diagnostics over the last two decades, invasive aspergillosis (IA) remains a devastating fungal disease. The number of immunocompromised patients hence vulnerable hosts increases, which is paralleled by emergence rise IA cases. Increased frequencies azole-resistant strains are reported from six continents, presenting new challenge for therapeutic management. Treatment options currently consist three classes antifungals (azoles, polyenes, echinocandins) with distinctive advantages shortcomings. Especially settings difficult to treat IA, comprising drug tolerance/resistance, limiting drug–drug interactions, and/or severe underlying organ dysfunction, novel approaches urgently needed. Promising drugs late-stage clinical development, including olorofim (a dihydroorotate dehydrogenase inhibitor), fosmanogepix Gwt1 enzyme ibrexafungerp triterpenoid), opelconazole (an azole optimized inhalation) rezafungin echinocandin long half-life time). Further, insights pathophysiology yielding immunotherapy as potential add-on therapy. Current investigations show encouraging results, so far mostly preclinical settings. In this review we discuss current strategies, give an outlook on possible pharmaceutical options, and, lastly, provide overview ongoing research IA.

Language: Английский

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In Vitro Assessment of Fluconazole and Cyclosporine A Antifungal Activities: A Promising Drug Combination Against Different Candida Species

Journal of Fungi, Journal Year: 2025, Volume and Issue: 11(2), P. 133 - 133

Published: Feb. 10, 2025

Invasive candidiasis is a common fungal infection associated with multiple risk factors, such as cancer, neutropenia, corticosteroid therapy, catheterization, and the use of broad-spectrum antibiotic treatment. Candida albicans predominant causative agent, although other species have been emerging in last years, together rise number strains resistant to currently available antifungal drugs, which poses challenge when treating these infections. Drug repurposing drug combinations are promising strategies for treatment invasive mycoses. In this study, we evaluated effect combination fluconazole (FLZ) cyclosporine A (CsA) against 39 clinical isolates reference Candida. Two methods, Loewe additivity model Bliss independence model, were used assess activity according CLSI EUCAST guidelines. The results demonstrated synergistic between 15–17 isolates, depending on evaluation used, including FLZ-resistant C. albicans, glabrata, parapsilosis, tropicalis. Notably, significantly reduced minimum inhibitory concentration (MIC) FLZ substantial those resistance FLZ. Additionally, time–kill curve studies confirmed interaction, further validating potential an alternative therapeutic strategy These findings emphasize importance investigating innovative address challenges posed by improve options

Language: Английский

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Candida auris in Dog Ears

Journal of Fungi, Journal Year: 2023, Volume and Issue: 9(7), P. 720 - 720

Published: June 30, 2023

Candida auris is an emerging global public health threat and resistant to most antifungal agents. Though fungi are significant pathogens for animals, the role of C. in animal remains unexplored. Here, we analysed microbial cultures skin ear swabs 87 dogs Delhi performed fungal meta-barcode sequencing samples 7 with confirmed otitis externa (OE). Overall, 4.5% (4/87) chronic infections contained evidence their canal (n = 3) on surface 1). Of three OE infection/colonisation, a diversity was observed, ITS sequence reads ranged from 0.06% 0.67%. Whole-genome six strains obtained culture two showed relatedness Clade I clinical strains. The report highlights isolation source; however, routes transmission this yeast significance between humans remain be investigated.

Language: Английский

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Activatable prodrug for controlled release of an antimicrobial peptide via the proteases overexpressed in Candida albicans and Porphyromonas gingivalis

Theranostics, Journal Year: 2024, Volume and Issue: 14(4), P. 1781 - 1793

Published: Jan. 1, 2024

Candida albicans and Porphyromonas gingivalis are prevalent in the subgingival area where frequency of fungal colonization increases with periodontal disease.Candida's transition to a pathogenic state its interaction P. exacerbate disease severity.However, current treatments for these infections differ, combined therapy remains unexplored.This work is based on an antimicrobial peptide that therapeutic induces color change nanoparticle reporter.Methods: We built characterized two enzyme-activatable prodrugs treat detect C. via controlled release peptide.The zwitterionic prodrug quenches peptide's activity until activation by protease inherent pathogens (SAP9 RgpB gingivalis).The toxicity intact was evaluated against fungal, bacterial, mammalian cells.Therapeutic efficacy assessed through microscopy, disk diffusion, viability assays, comparing alone.Finally, we developed colorimetric detection system aggregation plasmonic nanoparticles.Results: The showed negligible cells absent trigger.The impact comparable alone, minimum inhibitory concentration 3.1 -16 µg/mL.The enzymatic returned limit 10 nM gold nanoparticles 3 silver nanoparticles.Conclusion: This approach offers convenient selective sensing protease-induced treatment mechanism bioinspired peptides.

Language: Английский

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Advanced genetic techniques in fungal pathogen research

mSphere, Journal Year: 2024, Volume and Issue: 9(4)

Published: March 12, 2024

ABSTRACT Although fungi have been important model organisms for solving genetic, molecular, and ecological problems, recently, they are also becoming an source of infectious disease. Despite their high medical burden, fungal pathogens understudied, relative to other pathogenic microbes, less is known about how gene functions contribute This due, in part, a lack powerful genetic tools study these organisms. In turn, this has resulted inappropriate treatments diagnostics poor disease management. There variety reasons studies were challenging fungi, but recent years, most them overcome or advances made circumvent barriers. minireview, we highlight the discovery biology potential new antifungals created comprehensively pathogens.

Language: Английский

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Identifying new biomarkers of aggressive Group 3 and SHH medulloblastoma using 3D hydrogel models, single cell RNA sequencing and 3D OrbiSIMS imaging

Acta Neuropathologica Communications, Journal Year: 2023, Volume and Issue: 11(1)

Published: Jan. 11, 2023

Abstract The most common malignant brain tumour in children, medulloblastoma (MB), is subdivided into four clinically relevant molecular subgroups, although targeted therapy options informed by understanding of different cellular features are lacking. Here, comparing the aggressive subgroup (Group 3) with intermediate (SHH) subgroup, we identify crucial differences heterogeneity, including unique metabolism-driven subpopulations Group 3 and matrix-producing SHH. To analyse profiled individual nodules at level 3D MB hydrogel models, which recapitulate specific phenotypes, single cell RNA sequencing (scRNAseq) OrbiTrap Secondary Ion Mass Spectrometry (3D OrbiSIMS) imaging. In addition to identifying known metabolites characteristic MB, observed intra- internodular heterogeneity identified subgroup-specific subpopulations. We showed that extracellular matrix factors adhesion pathways defined SHH subpopulations, made up a distinct shell-like structure sulphur-containing species, comprising combination small leucine-rich proteoglycans (SLRPs) collagen organiser lumican. contrast, model was characterized multiple greatly enhanced oxidative phosphorylation tricarboxylic acid (TCA) cycle activity. Extensive TCA metabolite measurements revealed very high levels succinate fumarate malate almost undetectable particularly models. patients, (NMR spectroscopy) alongside activated stress response Nuclear Factor Erythroid 2-Related 2 (NRF2; gene expression analyses) were associated poorer survival. Based on these findings predicted confirmed NRF2 inhibition increased sensitivity vincristine long-term drug treatment assay MB. Thus, combining scRNAseq OrbiSIMS system able define elucidate new druggable biomarkers for low-risk

Language: Английский

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Healthcare-associated fungal infections and emerging pathogens during the COVID-19 pandemic

Frontiers in Fungal Biology, Journal Year: 2024, Volume and Issue: 5

Published: Feb. 23, 2024

Historically, fungi were mainly identified as plant and insect pathogens since they grow at 28°C. At the same time, bacteria are known to be most common human compatible with host body temperature of 37°C. Because immunocompromised hosts, cancer therapy, malnutrition, rapidly gaining attention pathogens. Over 150 million people have severe fungal infections, which lead approximately more than one deaths per year. Moreover, diseases like involving long-term therapy prophylactic use antifungal drugs in high-risk patients increased emergence drug-resistant fungi, including highly virulent strains such Candida auris . This clinical spectrum ranges from superficial mucocutaneous lesions life-threatening infections. review article summarizes effect hospital environments, especially during COVID-19 pandemic, on infections emerging The also provides insights into various their existing challenges, thereby driving need search for novel agents.

Language: Английский

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Fungal burden, dimorphic transition and candidalysin: Role in Candida albicans-induced vaginal cell damage and mitochondrial activation in vitro

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(5), P. e0303449 - e0303449

Published: May 20, 2024

Candida albicans ( C . ) can behave as a commensal yeast colonizing the vaginal mucosa, and in this condition is tolerated by epithelium. When epithelial tolerance breaks down, due to overgrowth hyphae formation, generated inflammatory response cell damage lead vulvovaginal candidiasis (VVC) symptoms. Here, we focused on induction of mitochondrial reactive oxygen species (mtROS) cells after infection involvement fungal burden, morphogenesis candidalysin (CL) production such induction. Bioluminescent (BLI) , PCA-2 529L strains were employed an vitro model including reconstituted epithelium (RVE), produced starting from A-431 line. The mtROS was kinetically measured using MitoSOX ™ Red probe. potency induced RVE proliferation have also been evaluated. induces rapid release cells, parallel with increase load hyphal formation. Under same experimental conditions, strain, known be defective CL production, minor showing key role causing mithocondrial activation. PCA-2, unable form hyphae, comparable but slower compared BLI yeasts. By reducing through ROS scavenger, increased burden observed during not cultures grown abiotic surface. Collectively, conclude that CL, more than seems play activation cell-damage are elements

Language: Английский

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Recombinant multiepitope proteins expressed in Escherichia coli cells and their potential for immunodiagnosis

Microbial Cell Factories, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 22, 2024

Recombinant multiepitope proteins (RMPs) are a promising alternative for application in diagnostic tests and, given their wide the most diverse diseases, this review article aims to survey use of these antigens diagnosis, as well discuss main points surrounding antigens. RMPs usually consisting linear, immunodominant, and phylogenetically conserved epitopes, has been applied experimental diagnosis various human animal such leishmaniasis, brucellosis, cysticercosis, Chagas disease, hepatitis, leptospirosis, leprosy, filariasis, schistosomiasis, dengue, COVID-19. The synthetic genes epitopes joined code single RMP, either with spacers or fused, different biochemical properties. epitopes' high density within contributes degree sensitivity specificity. can also sidestep need multiple peptide synthesis recombinant proteins, reducing costs enhancing standardization conditions immunoassays. Methods bioinformatics circular dichroism have widely development new RMPs, helping guide construction better understand structure. Several expressed, mainly using Escherichia coli expression system, highlighting importance cells biotechnological field. In fact, technological advances area, offering range strains be used, make used platform. experimentally diagnose broad illnesses laboratory, suggesting they could useful accurate diagnoses commercially. On point, RMP method offers tempting substitute production assemble commercial kits.

Language: Английский

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