The Hidden Fortress: A Comprehensive Review of Fungal Biofilms with Emphasis on Cryptococcus neoformans

Journal of Fungi, Год журнала: 2025, Номер 11(3), С. 236 - 236

Опубликована: Март 19, 2025

Biofilms are structurally organized communities of microorganisms that adhere to a variety surfaces. These produce protective matrices consisting polymeric polysaccharides, proteins, nucleic acids, and/or lipids promote shared resistance various environmental threats, including chemical, antibiotic, and immune insults. While algal bacterial biofilms more apparent in the scientific zeitgeist, many fungal pathogens also form biofilms. surprisingly common morphologically distinct from multicellular molds mushrooms normally associated with fungi instead an assemblage single-celled organisms. As collection yeast filamentous cells cloaked extracellular matrix, extreme threat public health, especially conjunction surgical implants. The encapsulated yeast, Cryptococcus neoformans, is opportunistic pathogen causes both pulmonary disseminated infections, particularly immunocompromised individuals. However, there emerging trend cryptococcosis among otherwise healthy C. neoformans forms diverse environments, within human hosts. Notably, biofilm association correlates increased expression multiple virulence factors host defenses antifungal treatments. Thus, it crucial develop novel strategies combat In this review, we discuss development treatment biofilms, particular focus on neoformans.

Язык: Английский

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Screening of drugs with potential antifungal activity for repurposing in the treatment of cryptococcosis

Letters in Applied Microbiology, Год журнала: 2025, Номер 78(4)

Опубликована: Март 25, 2025

Current therapeutic alternatives for the treatment of cryptococcosis are scarce, highly toxic, expensive and difficult to access. Therefore, aim this study was evaluate anticryptococcal potential a collection 27 drugs in vitro against several strains Cryptococcus neoformans gattii. We investigated parameters antifungal activity drugs: determination minimum inhibitory concentration (MIC), combinatorial effects with fluconazole, kinetics growth inhibition, post effect (PAFE) morphometric analyses at subinhibitory concentrations. Antiparasitics albendazole, fenbendazole, flubendazole, mebendazole antidepressants duloxetine paroxetine showed MIC 100 µmol L-1 or less most tested. The results zero-interaction power model indicated additive combination fluconazole finasteride, hydroxyzine paroxetine. combined treatments significantly improved ability kill C. ATCC H99. Same phenomenon occurred PAFE, as combinations suppressed fungal more effectively than alone. A significant reduction capsule size observed. Screening drug interesting results, benzimidazoles antiparasitics serotonin norepinephrine reuptake inhibitors foreground. Finasteride, vitro.

Язык: Английский

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Evaluation of the Synergistic Activity of Antimicrobial Peptidomimetics or Colistin Sulphate with Conventional Antifungals Against Yeasts of Medical Importance

Journal of Fungi, Год журнала: 2025, Номер 11(5), С. 370 - 370

Опубликована: Май 12, 2025

With rising multidrug-resistant yeast pathogens, conventional antifungals are becoming less effective, urging the need for adjuvants that enhance their activity at lower doses. This study evaluated synergistic of antimicrobial peptidomimetics (TM8 and RK758) or colistin sulphate in combination with against Candida albicans, C. tropicalis, parapsilosis, Meyerozyma guilliermondii, Nakaseomyces glabratus, Pichia kudriavzevii Kluyveromyces marxianus, Candidozyma auris using checkerboard microdilution test. RK758 was fluconazole 78% isolates, remaining 22% isolates still showing partial synergy; it showed synergy amphotericin B 56% caspofungin, exhibited either synergy. TM8 44% (with another 44%) 67% caspofungin isolates. Colistin No antagonism observed any combinations. Additionally, a time-kill assay further demonstrated between RK758. The effects these on cell membrane integrity were an ergosterol binding assay, supported by SYTOX Green cellular leakage assays, both indicating lytic effect. These results suggest can synergise antifungals, offering potential strategy therapy infections. likely plays role interaction thereby enhancing activities compounds sub-MIC levels.

Язык: Английский

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Targeting epigenetic regulators to overcome drug resistance in the emerging human fungal pathogen Candida auris

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Май 20, 2025

Abstract The rise of drug-resistant fungal species, such as Candida auris , poses a serious threat to global health, with mortality rates exceeding 40% and resistance surpassing 90%. limited arsenal effective antifungal agents underscores the urgent need for novel strategies. Here, we systematically evaluate role histone H3 post-translational modifications in C. drug resistance, focusing on acetylation mediated by Gcn5 Rtt109, methylation Set1, Set2, Dot1. Mutants deficient these enzymes exhibit varying degrees sensitivity. Notably, discover that GCN5 depletion subsequent loss downregulates key genes involved ergosterol biosynthesis efflux, resulting increased susceptibility azoles polyenes. Additionally, regulates cell wall integrity echinocandin through calcineurin signaling pathway transcription factor Cas5. In infection models using Galleria mellonella immunocompromised mice, deletion significantly reduces virulence . Furthermore, inhibitor CPTH 2 synergizes caspofungin vitro vivo without notable toxicity. These findings highlight critical pathogenicity positioning it promising therapeutic target combating invasive infections.

Язык: Английский

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Novel Therapeutic Approaches to Control Fungal Biofilms

Springer series on biofilms, Год журнала: 2025, Номер unknown, С. 239 - 279

Опубликована: Янв. 1, 2025

Язык: Английский

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Flexosomes as a promising nanoplatform for enhancing tolnaftate ocular delivery: Formulation, in vitro characterization, statistical optimization, ex vivo and microbial in vivo studies

International Journal of Pharmaceutics, Год журнала: 2023, Номер 646, С. 123471 - 123471

Опубликована: Окт. 2, 2023

Язык: Английский

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Report of endophthalmitis caused by Paradictyoarthrinium diffractum after plant trauma: A case involving left enucleation

International Journal of Infectious Diseases, Год журнала: 2024, Номер 146, С. 107117 - 107117

Опубликована: Май 26, 2024

Язык: Английский

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Reassessment of the role of combination antifungal therapy in the current era

Current Opinion in Infectious Diseases, Год журнала: 2024, Номер unknown

Опубликована: Сен. 11, 2024

Purpose of review Given the high mortality and morbidity associated with invasive fungal diseases (IFDs), use combination antifungal therapies is often considered despite dearth data. This aims to summarize current state literature therapies, discussing potential roles newer combinations key considerations for their clinical use. Recent findings In infections other than cryptococcal meningitis or in setting empirical treatment suspected azole-resistant Aspergillus infections, utility approaches remains controversial given paucity well designed randomized controlled trials. Data on combined treatments have been primarily limited in-vitro studies, animal models, case reports and/or observational studies. With availability novel agents (e.g. ibrexafungerp, fosmanogepix), therapy treat mould should be re-visited. A phase 2 trial ibrexafungerp voriconazole pulmonary aspergillosis on-going. Summary There a need investigate agents. includes delineating indication these determining how them most appropriately setting.

Язык: Английский

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Electrospun patches to deliver combination drug therapy for fungal infections

Frontiers in Drug Delivery, Год журнала: 2024, Номер 4

Опубликована: Сен. 16, 2024

Fungal infections, though affecting healthcare globally, receive insufficient attention in clinical and academic settings. Invasive fungal particularly caused by combat wounds, have been identified as a critical threat the US Department of Defense. Monotherapy with traditional antifungals is often insufficient, so combination therapies are explored to enhance treatment efficacy. However, systemic treatments can result severe adverse effects, suggesting need for localised delivery systems, such drug-loaded electrospun patches, administer directly infection site. This proof-of-concept study hypothesised that dual amorolfine terbinafine therapy slowly releasing from patches would be an effective way eradicating Candida albicans when patch was applied colony. The feasibility creating materials loaded antifungal investigated. Electrospinning used fabricate polycaprolactone (PCL) varying drug loadings (2.5%, 5%, 10% w/w) either individually or combination. incorporation both drugs fibres confirmed, predominantly amorphous state. Results showed had significantly greater prolonged effect compared monotherapy larger zones inhibition sustained efficacy over at least 7 days. therefore demonstrates PCL-based containing provide superior activity against C. patches. approach could lower required doses, reducing patient compliance due release, leading more therapy.

Язык: Английский

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Targeting epigenetic regulators to overcome drug resistance in the emerging human fungal pathogen Candida auris

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 21, 2024

The frequent use of antifungal agents has contributed to the emergence previously rare or unidentified drug-resistant fungal species, such as Candida auris, which presents mortality rates exceeding 40% and resistance surpassing 90%. rise life-threatening infections caused by these increasingly pathogens, coupled with limited arsenal effective agents, necessitates urgent development novel strategies combat multidrug resistance. In this study, we systematically evaluated role post-translational modifications (PTMs) histone H3 in drug C. focusing on acetylation mediated acetyltransferases Gcn5 Rtt109, well methylation methyltransferases Set1, Set2, Dot1. Mutants deficient enzymes exhibited varying degrees sensitivity. Notably, discovered that loss GCN5 subsequent downregulates key genes involved ergosterol biosynthesis efflux, resulting increased susceptibility major classes azoles polyenes. Additionally, regulates cell wall integrity echinocandin through modulation calcineurin signaling pathway transcription factor Cas5. invasive infection models using Galleria mellonella immunocompromised mice, deletion significantly reduced virulence auris. Furthermore, demonstrated inhibitor CPTH₂, when combined caspofungin (CAS), exhibits a synergistic effect against auris both in vitro vivo without significant toxicity human cells mice. conclusion, findings highlight critical pathogenicity positioning it promising therapeutic target for combating infections.

Язык: Английский

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