Comparative Analysis of the Aspergillus fumigatus Cell Wall Modification and Ensuing Human Dendritic Cell Responses by β-(1,3)-Glucan Synthase Inhibitors-Caspofungin and Enfumafungin.

Caspofungin, a lipopeptide, is an antifungal drug that belong to the class of echinocandin. It inhibits fungal cell wall β-(1,3)-glucan synthase activity and is the second-line of drug for invasive aspergillosis, a fatal infection caused mainly by Aspergillus fumigatus. On the other hand, Enfumafungin is a natural triterpene glycoside also with a β-(1,3)-glucan synthase inhibitory activity and reported to have antifungal potential.

CD56-mediated activation of human natural killer cells is triggered by Aspergillus fumigatus galactosaminogalactan.

Invasive aspergillosis causes significant morbidity and mortality in immunocompromised patients. Natural killer (NK) cells are pivotal for antifungal defense. Thus far, CD56 is the only known pathogen recognition receptor on NK cells triggering potent antifungal activity against Aspergillus fumigatus.

Kicking sleepers out of bed: Macrophages promote reactivation of dormant Cryptococcus neoformans by extracellular vesicle release and non-lytic exocytosis.

Macrophages play a key role in disseminated cryptococcosis, a deadly fungal disease caused by Cryptococcus neoformans. This opportunistic infection can arise following the reactivation of a poorly characterized latent infection attributed to dormant C. neoformans.

Distinct transcriptional responses to fludioxonil in Aspergillus fumigatus and its ΔtcsC and Δskn7 mutants reveal a crucial role for Skn7 in the cell wall reorganizations triggered by this antifungal.

Background: Aspergillus fumigatus is a major fungal pathogen that causes severe problems due to its increasing resistance to many therapeutic agents. Fludioxonil is a compound that triggers a lethal activation of the fungal-specific High Osmolarity Glycerol pathway. Its pronounced antifungal activity against A.

Solid-state NMR molecular snapshots of cell wall architecture during a conidial morphotype transition.

While establishing an invasive infection, the dormant conidia of transit through swollen and germinating stages, to form hyphae. During this morphotype transition, the conidial cell wall undergoes dynamic remodeling, which poses challenges to the host immune system and antifungal drugs. However, such cell wall reorganization during conidial germination has not been studied so far.

Protective role of host complement system in infection.

Invasive aspergillosis (IA) is a life-threatening fungal infection for immunocompromised hosts. It is, therefore, necessary to understand the immune pathways that control this infection. Although the primary infection site is the lungs, aspergillosis can disseminate to other organs through unknown mechanisms.

Surfactant protein D inhibits growth, alters cell surface polysaccharide exposure and immune activation potential of .

Humoral immunity plays a defensive role against invading microbes. However, it has been largely overlooked with respect to , an airborne fungal pathogen. Previously, we have demonstrated that surfactant protein D (SP-D), a major humoral component in human lung-alveoli, recognizes conidial surface exposed melanin pigment.

A glutathione-responsive silica-based nanosystem capped with in-situ polymerized cell-penetrating poly(disulfide)s for precisely modulating immuno-inflammatory responses.

Hypothesis: Precise modulation of immuno-inflammatory response is crucial to control periodontal diseases and related systemic comorbidities. The present nanosystem with the controlled-release and cell-penetrating manner enhances the inflammation modulation effects of baicalein in human gingival epithelial cells (hGECs) for better oral healthcare.

Experiments: We constructed a red-emissive mesoporous silica nanoparticle-based nanosystem with cell-penetrating poly(disulfide) (CPD) capping, through a facile in-situ polymerization approach.

Complement-Mediated Differential Immune Response of Human Macrophages to Species Through Interaction With Their Cell Wall Peptidorhamnomannans.

In this study, the human immune response mechanisms against and , two causative agents of human and animal sporotrichosis, were investigated. The interaction of and with human monocyte-derived macrophages (hMDMs) was shown to be dependent on the thermolabile serum complement protein C3, which facilitated the phagocytosis of yeast cells through opsonization. The peptidorhamnomannan (PRM) component of the cell walls of these two yeasts was found to be one of their surfaces exposed pathogen-associated molecular pattern (PAMP), leading to activation of the complement system and deposition of C3b on the yeast surfaces.

extracellular vesicles properties and their use as vaccine platforms.

Whereas extracellular vesicle (EV) research has become commonplace in different biomedical fields, this field of research is still in its infancy in mycology. Here we provide a robust set of data regarding the structural and compositional aspects of EVs isolated from the fungal pathogenic species and . Using cutting-edge methodological approaches including cryogenic electron microscopy and cryogenic electron tomography, proteomics, and flow cytometry, we revisited cryptococcal EV features and suggest a new EV structural model, in which the vesicular lipid bilayer is covered by mannoprotein-based fibrillar decoration, bearing the capsule polysaccharide as its outer layer.

Proteomic Analysis of Humoral Immune Components in Bronchoalveolar Lavage of Patients Infected or Colonized by .

Humoral immune components have been individually studied in the context of interaction of host with , a major airborne fungal pathogen. However, a global view of the multitude and complex nature of humoral immune components is needed to bring new insight into host- interaction. Therefore, we undertook comparative proteomic analysis of the bronchoalveolar lavage fluid collected from individuals infected or colonized with versus controls, to identify those alveolar humoral components affected upon infection.

The Proteome of Community Living Is Differentially Modulated by the Morphologic and Structural Features of the Bacterial Cohabitants.

is a commensal polymorphic and opportunistic fungus, which usually resides as a small community in the oral cavities of a majority of humans. The latter eco-system presents this yeast varied opportunities for mutualistic interactions with other cohabitant oral bacteria, that synergizes its persistence and pathogenicity. Collectively, these communities live within complex plaque biofilms which may adversely affect the oral health and increase the proclivity for oral candidiasis.

The Role of RodA-Conserved Cysteine Residues in the Conidial Surface Organization.

Immune inertness of conidia is attributed to its surface rodlet-layer made up of RodAp, characterized by eight conserved cysteine residues forming four disulfide bonds. Earlier, we showed that the conserved cysteine residue point (ccrp mutations result in conidia devoid of the rodlet layer. Here, we extended our study comparing the surface organization and immunoreactivity of conidia carrying ccrp-mutations with the deletion mutant (∆).

Differential Interactions of Serum and Bronchoalveolar Lavage Fluid Complement Proteins with Conidia of Airborne Fungal Pathogen Aspergillus fumigatus.

Even though both cellular and humoral immunities contribute to host defense, the role played by humoral immunity against the airborne opportunistic fungal pathogen has been underexplored. In this study, we aimed at deciphering the role of the complement system, the major humoral immune component, against Mass spectrometry analysis of the proteins extracted from conidial (asexual spores and infective propagules) surfaces opsonized with human serum indicated that C3 is the major complement protein involved. Flow cytometry and immunolabeling assays further confirmed C3b (activated C3) deposition on the conidial surfaces.

Aspergillus fumigatus Transcription Factors Involved in the Caspofungin Paradoxical Effect.

is the leading cause of pulmonary fungal diseases. Azoles have been used for many years as the main antifungal agents to treat and prevent invasive aspergillosis. However, in the last 10 years there have been several reports of azole resistance in and new strategies are needed to combat invasive aspergillosis.

Infection in Humans With STAT3-Deficiency Is Associated With Defective Interferon-Gamma and Th17 Responses.

In humans, loss-of-function mutation in the gene is frequently associated with susceptibility to bacterial as well as fungal infections including aspergillosis, although its pathogenesis remains largely unknown. In the present study, we investigated the immune responses obtained after stimulation with in STAT3-deficient patients. conidial killing efficiencies of both monocytes and neutrophils isolated from whole blood samples of STAT3-deficient patients were not different compared to those of healthy controls.

Potential of Chemically Synthesized Oligosaccharides To Define the Carbohydrate Moieties of the Fungal Cell Wall Responsible for the Human Immune Response, Using Aspergillus fumigatus Galactomannan as a Model.

Methodologies to identify epitopes or ligands of the fungal cell wall polysaccharides influencing the immune response of human pathogens have to date been imperfect. Using the galactomannan (GM) of as a model, we have shown that synthetic oligosaccharides of distinct structures representing key fragments of cell wall polysaccharides are the most precise tools to study the serological and immunomodulatory properties of a fungal polysaccharide.

Red-Emissive Guanylated Polyene-Functionalized Carbon Dots Arm Oral Epithelia against Invasive Fungal Infections.

Oral candidiasis as a highly prevalent and recurrent infection in medically compromised individuals is mainly caused by the opportunistic fungal pathogen . This epithelial infection, if not controlled effectively, can progress to life-threatening systemic conditions and complications. The efficacy of current frontline antifungals is limited due to their poor bioavailability and systemic toxicity.

β-Glucan Grafted Microcapsule, a Tool for Studying the Immunomodulatory Effect of Microbial Cell Wall Polysaccharides.

β-(1,3)-Glucan is one of the antigenic components of the bacterial as well as fungal cell wall. We designed microcapsules (MCs) ligated with β-(1,3)-glucan, to study its immunomodulatory effect. The MCs were obtained by interfacial polycondensation between diacyl chloride (sebacoyl chloride and terephtaloyl chloride) and diethylenetriamine in organic and aqueous phases, respectively.

Novel mouse monoclonal antibodies specifically recognizing β-(1→3)-D-glucan antigen.

β-(1→3)-D-Glucan is an essential component of the fungal cell wall. Mouse monoclonal antibodies (mAbs) against synthetic nona-β-(1→3)-D-glucoside conjugated with bovine serum albumin (BSA) were generated using hybridoma technology. The affinity constants of two selected mAbs, 3G11 and 5H5, measured by a surface plasmon resonance biosensor assay using biotinylated nona-β-(1→3)-D-glucan as the ligand, were approximately 11 nM and 1.

Chemical Synthesis and Application of Biotinylated Oligo-α-(1 → 3)-d-Glucosides To Study the Antibody and Cytokine Response against the Cell Wall α-(1 → 3)-d-Glucan of Aspergillus fumigatus.

Biotinylated hepta-, nona- and undeca-α-(1 → 3)-d-glucosides representing long oligosaccharides of α-(1 → 3)-d-glucan, one of the major components of the cell walls of the fungal pathogen Aspergillus fumigatus, were synthesized for the first time via a blockwise strategy. Convergent assembly of the α-(1 → 3)-d-glucan chains was achieved by glycosylation with oligoglucoside derivatives bearing 6- O-benzoyl groups. Those groups are capable of remote α-stereocontrolling participation, making them efficient α-directing tools even in the case of large glycosyl donors.

conidial metalloprotease Mep1p cleaves host complement proteins.

Innate immunity in animals including humans encompasses the complement system, which is considered an important host defense mechanism against , one of the most ubiquitous opportunistic human fungal pathogens. Previously, it has been shown that the alkaline protease Alp1p secreted from mycelia degrades the complement components C3, C4, and C5. However, it remains unclear how the fungal spores ( conidia) defend themselves against the activities of the complement system immediately after inhalation into the lung.