Conidial surface proteins at the interface of fungal infections

Blango, Matthew G.; Kniemeyer, Olaf; Brakhage, Axel A.

doi:10.1371/journal.ppat.1007939

Cited by 26 publications

(31 citation statements)

References 47 publications

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“…S2A-B). When we compared afEV formation induced by stimulation of PMNs with wt and pksP mutant conidia, which lack the pigment and virulence determinant dihydroxynaphthalene melanin (25, 40–43), we discovered that melanin-deficient conidia doubled the production of EVs (Fig. 1C-E).…”

Section: Resultsmentioning

confidence: 99%

Human neutrophils produce antifungal extracellular vesicles againstAspergillus fumigatus

Shopova

Belyaev

Dasari

et al. 2019

Preprint

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AbstractPolymorphonuclear granulocytes (PMNs) are indispensable for controlling life-threatening fungal infections. In addition to various effector mechanisms, PMNs also produce extracellular vesicles (EVs). Their contribution to antifungal defense has remained unexplored. We reveal that the clinically important human pathogenic fungus Aspergillus fumigatus triggers PMNs to release a distinct set of antifungal EVs (afEVs). Proteome analyses indicated that afEVs are enriched in antimicrobial proteins. The cargo and release kinetics of EVs are modulated by the fungal strain confronted. Tracking of afEVs indicated that they associated with fungal cells and even entered fungal hyphae, resulting in alterations in the morphology of the fungal cell wall and dose-dependent antifungal effects. Two human proteins enriched in afEVs, cathepsin G and azurocidin, were heterologously expressed in fungal hyphae, which led to reduced fungal growth relative to a control retinol binding protein 7 producing strain. In conclusion, the production of afEVs by PMNs offers an intriguing, previously overlooked mechanism of antifungal defense against A. fumigatus.ImportanceInvasive fungal infections caused by the mold Aspergillus fumigatus are a growing concern in the clinic due to the increasing use of immunosuppressive therapies and increasing antifungal drug resistance. These infections result in high mortality as treatment and diagnostic options remain limited. In healthy individuals, neutrophilic granulocytes are critical for elimination of A. fumigatus from the host; however, the exact extracellular mechanism of neutrophil-mediated antifungal activity remains unresolved. Here, we present a mode of antifungal defense employed by human neutrophils against A. fumigatus not previously described. We find that extracellular vesicles produced by neutrophils in response to A. fumigatus infection are able to associate with the fungus, limit growth, and elicit cell damage by delivering antifungal cargo. In the end, antifungal extracellular vesicle biology provides a significant step forward in our understanding of A. fumigatus host pathogenesis and opens up novel diagnostic and therapeutic possibilities.

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Section: Resultsmentioning

confidence: 99%

Human neutrophils produce antifungal extracellular vesicles againstAspergillus fumigatus

Shopova

Belyaev

Dasari

et al. 2019

Preprint

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“…Although conidia attachment is nonspecific, sites that encourage invasion differ by insect host. Host attachment of the fungi is determined by the influence of conidia hydrophobic surface proteins (Blango et al, 2019; Ortiz‐Urquiza & Keyhani, 2013).…”

Section: Attachment Of Conidia On Hostmentioning

confidence: 99%

“…After conquering host insects, conidia regenerated on the host surface are mainly dispersed by nonbiological factors, such as water and wind (Zimmermann, 2007). The hydrophobic property of conidia is not only necessary to attach to the host cuticle and achieve successful infection, but also to facilitate dispersion with water (Blango et al, 2019). Studies on biological dispersion of conidia have been reported for the phylum Zoopagomycota.…”

Section: Transmission and Dispersalmentioning

confidence: 99%

Pathogenesis‐related genes of entomopathogenic fungi

Shin

Lee

Park

et al. 2020

Arch Insect Biochem Physiol

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All living things on Earth experience various diseases such as those caused by viruses, bacteria, and fungi. Insects are no exception to this rule, and fungi that cause disease in insects are called entomopathogenic fungi. These fungi have been developed as microbial insecticides and are used to control various pests. Generally, the mode of action of entomopathogenic fungi is divided into the attachment of conidia, germination, penetration, growth, and generation of secondary infectious conidia. In each of these steps, that entomopathogenic fungi use genes in a complex manner (specific or diverse) has been shown by gene knockout and RNA-sequencing analysis. In this review, the information mechanism of entomopathogenic fungi was divided into six steps: (1) attachment of conidia to host, (2) germination and appressorium, (3) penetration, (4) fungal growth in hemolymph, (5) conidia production on host, and (6) transmission and dispersal. The strategy used by the fungi in each step was described at the genetic level. In addition, an approach for studying the mode of action of the fungi is presented.

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“…The A. fumigatus cell wall not only maintains cellular integrity and protects the cell from external aggression but also serves as a harbor for virulence factors that contribute to immune evasion, adherence, and virulence ( 8 ). Although the cell wall is composed of >90% polysaccharides ( 1 ), hundreds of different surface proteins have been detected across various proteome studies ( 9 – 11 ).…”

Section: Introductionmentioning

confidence: 99%

Biotinylated Surfome Profiling Identifies Potential Biomarkers for Diagnosis and Therapy of Aspergillus fumigatus Infection

Jia

Krüger

Blango

et al. 2020

mSphere

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Aspergillus fumigatus is one of the most common airborne molds capable of causing mycoses and allergies in humans. During infection, fungal surface proteins mediate the first contact with the human immune system to evade immune responses or to induce hypersensitivity. Several methods have been established for surface proteomics (surfomics). Biotinylation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identification of peptides is a particularly efficient method to identify the surface-exposed regions of proteins that potentially mediate interaction with the host. After biotinylation of surface proteins during spore germination, we detected 231 different biotinylated surface proteins (including several well-known proteins such as RodA, CcpA, and DppV; allergens; and heat shock proteins [HSPs]), as well as some previously undescribed surface proteins. The dynamic change of the surface proteome was illustrated by detection of a relatively high number of proteins exclusively at one developmental stage. Using immunofluorescence microscopy, we confirmed the surface localization of several HSPs of the HSP70 family, which may have moonlighting functions. Collectively, by comparing our data with data representative of previously published A. fumigatus surface proteomes, our study generated a comprehensive data set corresponding to the A. fumigatus surfome and uncovered the surface-exposed regions of many proteins on the surface of conidia or hyphae. These surface-exposed regions are candidates for direct interaction with host cells and may represent antigenic epitopes that either induce protective immune responses or mediate immune evasion. Thus, our data sets provided and compiled here represent reasonable immunotherapy and diagnostic targets for future investigations. IMPORTANCE Aspergillus fumigatus is the most important airborne human-pathogenic mold, capable of causing both life-threatening invasive pulmonary aspergillosis in immunocompromised patients and allergy-inducing infections in individuals with atopic allergy. Despite its obvious medical relevance, timely diagnosis and efficient antifungal treatment of A. fumigatus infection remain major challenges. Proteins on the surface of conidia (asexually produced spores) and mycelium directly mediate host-pathogen interaction and also may serve as targets for diagnosis and immunotherapy. However, the similarity of protein sequences between A. fumigatus and other organisms, sometimes even including the human host, makes selection of targets for immunological-based studies difficult. Here, using surface protein biotinylation coupled with LC-MS/MS analysis, we identified hundreds of A. fumigatus surface proteins with exposed regions, further defining putative targets for possible diagnostic and immunotherapeutic design.

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Conidial surface proteins at the interface of fungal infections

Cited by 26 publications

References 47 publications

Human neutrophils produce antifungal extracellular vesicles againstAspergillus fumigatus

Human neutrophils produce antifungal extracellular vesicles againstAspergillus fumigatus

Pathogenesis‐related genes of entomopathogenic fungi

Biotinylated Surfome Profiling Identifies Potential Biomarkers for Diagnosis and Therapy of Aspergillus fumigatus Infection

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