Global fungal-host interactome mapping identifies host targets of candidalysin

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 27, 2024

Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map interactome of all eight Ece1 peptides with their direct protein and identified list potential interacting proteins, some which were shared between peptides. CCNH, regulatory subunit CDK-activating kinase (CAK) complex involved in DNA damage repair, was as one host candidalysin. Mechanistic studies revealed that candidalysin triggers significantly increased double-strand breaks (DSBs), evidenced formation γ-H2AX foci colocalization CCNH γ-H2AX. Importantly, binds directly activate CAK inhibit repair pathway. Loss alleviates DSBs under treatment. Depletion candidalysin-encoding gene fails induce stimulates upregulation murine model oropharyngeal candidiasis. Collectively, our study reveals acts hijack canonical pathway targeting promote infection.

Language: Английский

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Antifungal activity of clinical Lactobacillus strains against Candida albicans biofilms: identification of potential probiotic candidates to prevent oral candidiasis

Biofouling, Journal Year: 2018, Volume and Issue: 34(2), P. 212 - 225

Published: Jan. 30, 2018

This study isolated Lactobacillus strains from caries-free subjects and evaluated the inhibitory effects directly on three of C. albicans, two clinical one reference strain. Thirty were for antimicrobial activity against in vitro albicans biofilms. L. paracasei 28.4, rhamnosus 5.2 fermentum 20.4 isolates exhibited most significant albicans. Co-incubation between these microorganisms resulted deterrence biofilm development retardation hyphal formation. The hindrance was characterized by downregulated expression biofilm-specific genes (ALS3, HWP1, EFG1 CPH1). demonstrated ability to exert antifungal through inhibition

Language: Английский

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Extracellular proteinases of Candida species pathogenic yeasts

Molecular Oral Microbiology, Journal Year: 2017, Volume and Issue: 33(2), P. 113 - 124

Published: Nov. 15, 2017

The increased incidence of severe disseminated infections caused by the opportunistic yeast-like fungi Candida spp. highlights urgent need for research into major virulence factors these pathogens-extracellular aspartic proteinases candidapepsin and yapsin families. Classically, enzymes were considered to be generally destructive that damage host tissues provide nutrients pathogen propagation. However, in recent decades, novel more specific functions have been suggested extracellular candidal proteinases. These include contributions cell wall maintenance remodeling, formation polymicrobial biofilms, adhesion external protective barriers host, deregulation proteolytic cascades (such as complement system, blood coagulation kallikrein-kinin system), a dysregulated proteinase-inhibitor balance, inactivation antimicrobial peptides, evasion immune responses induction inflammatory mediator release from cells. Only few activities recognized albicans candidapepsins also confirmed other species, characterization glabrata yapsins remains limited.

Language: Английский

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Antifungal Compounds againstCandidaInfections from Traditional Chinese Medicine

BioMed Research International, Journal Year: 2017, Volume and Issue: 2017, P. 1 - 12

Published: Jan. 1, 2017

Infections caused by Candida albicans , often refractory and with high morbidity mortality, cause a heavy burden on the public health while current antifungal drugs are limited associated toxicity resistance. Many plant-derived molecules including compounds isolated from traditional Chinese medicine (TCM) reported to have activity through different targets such as cell membrane, wall, mitochondria, virulence factors. Here, we review recent progress in anti- TCM, well their mechanisms. Considering diverse structures, TCM might be potential library for drug development.

Language: Английский

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Scalar nanostructure of the Candida albicans cell wall; a molecular, cellular and ultrastructural analysis and interpretation

The Cell Surface, Journal Year: 2020, Volume and Issue: 6, P. 100047 - 100047

Published: Nov. 9, 2020

Despite the importance of fungal cell walls as principle determinant morphology and defining element determining interactions with other cells, few scalar models have been developed that reconcile chemical microscopic attributes its structure. The wall pathogen Candida albicans is comprised an amorphous inner skeletal layer β(1,3)- β(1,6)-glucan chitin outer fibrillar thought to be dominated by highly mannosylated proteins. architecture these two layers can resolved at electron microscopy level, but visualised structure has not yet defined precisely in terms. We therefore examined precise structure, location molecular sizes components using transmission tomography tested predictions mutants agents perturb normal demonstrate fibrils are a frond N-linked chain mannans linked basal GPI-proteins concentrated mid-wall region non-elastic microfibrils cantilevered sufficient lengths non-fibrillar and/or β-glucan enable chitin-glucan cage flex, e.g. during morphogenesis osmotic swelling. present first three-dimensional nano-scalar model C. which used test hypotheses relating structure–function relationships underpin pathobiology this pathogen.

Language: Английский

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The Cell Biology of the Trichosporon-Host Interaction

Frontiers in Cellular and Infection Microbiology, Journal Year: 2017, Volume and Issue: 7

Published: April 7, 2017

Fungi of the genus Trichosporon are increasingly recognized as causative agents superficial and invasive fungal disease in humans. Although most species considered commensals human skin gastrointestinal tract, these basidiomycetes an increasing cause among immunocompromised hosts, such hematological patients solid organ transplant recipients. The initiation commensal or pathogenic programs by spp. involves adaptation to host microenvironment its immune system. However, exact virulence factors activated upon transition a lifestyle, including intricate biology cell wall, how interact with subvert responses remain largely unknown. Here, we revisit our current understanding attributes spp., particularly T. asahii, their interaction system, accommodate this knowledge within novel perspectives on diagnostics therapeutics.

Language: Английский

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Silver Nanoparticles Addition in Poly(Methyl Methacrylate) Dental Matrix: Topographic and Antimycotic Studies

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(19), P. 4691 - 4691

Published: Sept. 21, 2019

The widespread use of nanoparticles (NPs) in medical devices has opened a new scenario the treatment and prevention many diseases infections owing to unique physico-chemical properties NPs. In this way, silver (AgNPs) are known have strong antimicrobial activity, even at low concentrations, due their ability selectively destroy cellular membranes. particular, field dental medicine, AgNPs different kinds prosthesis matrixes could be fundamental tool immunodepressed patients that suffer oral infections. Candida albicans (C. albicans), an opportunistic pathogenic yeast with high colonization ability, is one causative agents cavity infection. our work, we added monodispersed citrate-capping size 20 nm two concentrations (3 wt% 3.5 wt%) poly(methyl methacrylate) (PMMA), common resin used develop prostheses. After characterization, evaluated topographical modification PMMA addition by means atomic force microscopy (AFM), showing reduction surface roughness. C. on surfaces was assessed Miles Misra technique as well scanning electron (SEM) 24 h 48 encouraging results viability after exposure.

Language: Английский

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Mannan detecting C-type lectin receptor probes recognise immune epitopes with diverse chemical, spatial and phylogenetic heterogeneity in fungal cell walls

PLoS Pathogens, Journal Year: 2020, Volume and Issue: 16(1), P. e1007927 - e1007927

Published: Jan. 30, 2020

During the course of fungal infection, pathogen recognition by innate immune system is critical to initiate efficient protective responses. The primary event that triggers responses binding Pattern Recognition Receptors (PRRs), which are expressed at surface host cells, Pathogen-Associated Molecular Patterns (PAMPs) located predominantly in cell wall. Most fungi have mannosylated PAMPs their walls and these recognized a range C-type lectin receptors (CTLs). However, precise spatial distribution ligands induce within not well defined. We used recombinant IgG Fc-CTLs fusions three murine mannan detecting CTLs, including dectin-2, mannose receptor (MR) carbohydrate domains (CRDs) 4-7 (CRD4-7), human DC-SIGN (hDC-SIGN) β-1,3 glucan-binding dectin-1 map PRR wall grown vitro rich minimal media. show epitopes mannan-specific CTL can be clustered or diffuse, superficial buried inner demonstrate do correlate with phylogenetic relationships between fungi, Fc-lectin discriminated mannosides on different morphologies same fungus. also epitope differentiation during phases growth cycle Candida albicans MR labelled outer chain N-mannans whilst dectin-2 core displayed deeper These maps cells therefore reveal remarkable spatial, temporal chemical diversity, indicating triggering events originates from multiple physical origins surface.

Language: Английский

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Differences in fungal immune recognition by monocytes and macrophages: N-mannan can be a shield or activator of immune recognition

The Cell Surface, Journal Year: 2020, Volume and Issue: 6, P. 100042 - 100042

Published: July 21, 2020

We designed experiments to assess whether fungal cell wall mannans function as an immune shield or agonist. Fungal β-(1,3)-glucan normally plays a major and dominant role in activation. The outer mannan layer has been variously described shield, because it the potential mask underlying β-(1,3)-glucan, activator, also engage with wide range of mannose detecting PRRs. To resolve this conundrum we examined species-specific differences host recognition och1Δ N-mannosylation-deficient mutant background four species yeast-like fungi. Irrespective species, cytokine response (TNFα IL-6) induced by mutants human monocytes was reduced compared that wild type. In contrast, TNFα production increased, relative type, due increased β-glucan exposure, when mouse macrophages were used. These observations suggest N-mannan is not PAMP for these cells does fungus from inner β-glucan. However, significant inducer monocytes. Therefore metaphor "mannan shield" can only be applied some, but all, myeloid used profiling species.

Language: Английский

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Chemical Composition and Antimicrobial Activity of a New Olive Pomace Functional Ingredient

Pharmaceuticals, Journal Year: 2021, Volume and Issue: 14(9), P. 913 - 913

Published: Sept. 10, 2021

Olive pomace, an olive oil processing byproduct, can be upcycled and meet the current demand for natural sustainable food ingredients. In this work, a patented process was used to obtain functional ingredient from different pomaces. The nutritional, chemical antioxidant profiles, as well antimicrobial activity against S. aureus, E. coli C. albicans, were investigated first time. amount of phenolics ranged between 3.1 3.8 g gallic acid eq./100 in all samples flavonoids 2.0 3.2 catechin eq/100 g. No significant differences found regarding activity. total fat varied 5 11%, α-tocopherol being major vitamer oleic main fatty acid. protein ash contents 1–4% 10–17%, respectively. with higher hydroxytyrosol content (220 mg/100 g) also presented best minimal inhibitory concentration tested bacteria. albicans verified. This new presents potential preservative or nutritional profile enhancer. Moreover, it advantageous products, since comprises specific lipid hydrophilic bioactive compounds usually not present other plant extracts.

Language: Английский

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