Cryptococcus gattii polysaccharide capsule: An insight on fungal‐host interactions and vaccine studies

ABSTRACTThe yeast-like pathogenCryptococcus gattiiis an etiological agent of cryptococcosis. The major cryptococcal virulence factor is the polysaccharide capsule, which is composed of glucuronoxylomannan (GXM), galactoxylomannan (GalXM), and mannoproteins (MPs). The GXM and GalXM polysaccharides have been extensively characterized; however, there is little information about the role of mannoproteins in capsule assembly and their participation in yeast pathogenicity. The present study characterized the function of a predicted mannoprotein fromC. gattii, designated Krp1. Loss-of-function and gain-of-function mutants were generated, and phenotypes associated with the capsular architecture were evaluated. The null mutant cells were more sensitive to a cell wall stressor that disrupts beta-glucan synthesis. Also, these cells displayed increased GXM release to the culture supernatant than the wild-type strain did. The loss of Krp1 influenced cell-associated cryptococcal polysaccharide thickness and phagocytosis by J774.A1 macrophages in the early hours of interaction, but no difference in virulence in a murine model of cryptococcosis was observed. In addition, recombinant Krp1 was antigenic and differentially recognized by serum from an individual with cryptococcosis, but not with serum from an individual with candidiasis. Taken together, these results indicate thatC. gattiiKrp1 is important for the cell wall structure, thereby influencing capsule assembly, but is not essential for virulencein vivo.IMPORTANCECryptococcus gattiihas the ability to escape from the host’s immune system through poorly understood mechanisms and can lead to the death of healthy individuals. The role of mannoproteins inC. gattiipathogenicity is not completely understood. The present work characterized a protein, Kpr1, that is essential for the maintenance ofC. gattiimain virulence factor, the polysaccharide capsule. Our data contribute to the understanding of the role of Kpr1 in capsule structuring, mainly by modulating the distribution of glucans inC. gattiicell wall.

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Iron and siderophores in fungal–host interactions

Mycological Research ◽

10.1016/j.mycres.2007.11.012 ◽

2008 ◽

Vol 112 (2) ◽

pp. 170-183 ◽

Cited By ~ 98

Author(s):

Linda Johnson

Keyword(s):

Fungal Host ◽

Host Interactions

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In vitro infection models to study fungal-host interactions

FEMS Microbiology Reviews ◽

10.1093/femsre/fuab005 ◽

2021 ◽

Author(s):

Antonia Last ◽

Michelle Maurer ◽

Alexander S Mosig ◽

Mark S Gresnigt ◽

Bernhard Hube

Keyword(s):

Fungal Infections ◽

In Vitro Models ◽

Fungal Host ◽

Host Interactions ◽

Mucosal Surfaces ◽

Life Threatening ◽

On Chip ◽

Fungal Interactions

Abstract Fungal infections (mycoses) affect over a billion people per year. Approximately two million of these infections are life-threatening, especially for patients with a compromised immune system. Fungi of the genera Aspergillus, Candida, Histoplasma, and Cryptococcus are opportunistic pathogens that contribute to a substantial number of mycoses. To optimize the diagnosis and treatment of mycoses, we need to understand the complex fungal-host interplay during pathogenesis, the fungal attributes causing virulence, and how the host resists infection via immunological defenses. In vitro models can be used to mimic fungal infections of various tissues and organs and the corresponding immune responses at near-physiological conditions. Furthermore, models can include fungal interactions with the host-microbiota to mimic the in vivo situation on skin and mucosal surfaces. This article reviews currently used in vitro models of fungal infections ranging from cell monolayers to microfluidic 3D organ-on-chip (OOC) platforms. We also discuss how OOC models can expand the toolbox for investigating interactions of fungi and their human hosts in the future.

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Fluconazole Alters the Polysaccharide Capsule of Cryptococcus gattii and Leads to Distinct Behaviors in Murine Cryptococcosis

PLoS ONE ◽

10.1371/journal.pone.0112669 ◽

2014 ◽

Vol 9 (11) ◽

pp. e112669 ◽

Cited By ~ 21

Author(s):

Julliana Ribeiro Alves Santos ◽

Rodrigo Assunção Holanda ◽

Susana Frases ◽

Mayara Bravim ◽

Glauber de S. Araujo ◽

...

Keyword(s):

Cryptococcus Gattii ◽

Polysaccharide Capsule

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A Computational Protocol to Analyze Metatranscriptomic Data Capturing Fungal–Host Interactions

Methods in Molecular Biology - Plant Pathogenic Fungi and Oomycetes ◽

10.1007/978-1-4939-8724-5_15 ◽

2018 ◽

pp. 207-233 ◽

Cited By ~ 1

Author(s):

Yong Zhang ◽

Li Guo ◽

Li-Jun Ma

Keyword(s):

Fungal Host ◽

Host Interactions ◽

Data Capturing ◽

Computational Protocol

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Mannitol metabolism during pathogenic fungal–host interactions under stressed conditions

Frontiers in Microbiology ◽

10.3389/fmicb.2015.01019 ◽

2015 ◽

Vol 6 ◽

Cited By ~ 39

Author(s):

Mukesh Meena ◽

Vishal Prasad ◽

Andleeb Zehra ◽

Vijai K. Gupta ◽

Ram S. Upadhyay

Keyword(s):

Fungal Host ◽

Host Interactions ◽

Mannitol Metabolism

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Transcriptome Profiling Data of Botrytis cinerea Infection on Whole Plant Solanum lycopersicum

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-05-20-0109-a ◽

2020 ◽

Vol 33 (9) ◽

pp. 1103-1107 ◽

Cited By ~ 2

Author(s):

Dhruv Aditya Srivastava ◽

Gulab Chand Arya ◽

Eswari PJ Pandaranayaka ◽

Ekaterina Manasherova ◽

Dov B. Prusky ◽

...

Keyword(s):

Botrytis Cinerea ◽

Solanum Lycopersicum ◽

Model Organism ◽

Transcriptome Profiling ◽

Infection Process ◽

Future Research ◽

Fungal Host ◽

Host Interactions ◽

Whole Plant ◽

Gene Count

Botrytis cinerea is a foliar necrotrophic fungal-pathogen capable of infecting >580 genera of plants, is often used as model organism for studying fungal-host interactions. We used RNAseq to study transcriptome of B. cinerea infection on a major (worldwide) vegetable crop, tomato (Solanum lycopersicum). Most previous works explored only few infection stages, using RNA extracted from entire leaf-organ diluting the expression of studied infected region. Many studied B. cinerea infection, on detached organs assuming that similar defense/physiological reactions occurs in the intact plant. We analyzed transcriptome of the pathogen and host in 5 infection stages of whole-plant leaves at the infection site. We supply high quality, pathogen-enriched gene count that facilitates future research of the molecular processes regulating the infection process.

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Active Fungal Communities in Asymptomatic Eucalyptus grandis Stems Differ between a Susceptible and Resistant Clone

Microorganisms ◽

10.3390/microorganisms7100375 ◽

2019 ◽

Vol 7 (10) ◽

pp. 375

Author(s):

Mandy Messal ◽

Bernard Slippers ◽

Sanushka Naidoo ◽

Oliver Bezuidt ◽

Martin Kemler

Keyword(s):

Molecular Mechanisms ◽

Eucalyptus Grandis ◽

Fungal Communities ◽

Biological Functions ◽

Fungal Host ◽

Host Interactions ◽

Plant Parts ◽

Significant Difference ◽

Microbe Interactions ◽

Plant Transcriptome

Fungi represent a common and diverse part of the microbial communities that associate with plants. They also commonly colonise various plant parts asymptomatically. The molecular mechanisms of these interactions are, however, poorly understood. In this study we use transcriptomic data from Eucalyptus grandis, to demonstrate that RNA-seq data are a neglected source of information to study fungal–host interactions, by exploring the fungal transcripts they inevitably contain. We identified fungal transcripts from E. grandis data based on their sequence dissimilarity to the E. grandis genome and predicted biological functions. Taxonomic classifications identified, amongst other fungi, many well-known pathogenic fungal taxa in the asymptomatic tissue of E. grandis. The comparison of a clone of E. grandis resistant to Chrysoporthe austroafricana with a susceptible clone revealed a significant difference in the number of fungal transcripts, while the number of fungal taxa was not substantially affected. Classifications of transcripts based on their respective biological functions showed that the fungal communities of the two E. grandis clones associate with fundamental biological processes, with some notable differences. To shield the greater host defence machinery in the resistant E. grandis clone, fungi produce more secondary metabolites, whereas the environment for fungi associated with the susceptible E. grandis clone is more conducive for building fungal cellular structures and biomass growth. Secreted proteins included carbohydrate active enzymes that potentially are involved in fungal–plant and fungal–microbe interactions. While plant transcriptome datasets cannot replace the need for designed experiments to probe plant–microbe interactions at a molecular level, they clearly hold potential to add to the understanding of the diversity of plant–microbe interactions.

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Fungal-host interactions: insights into microRNA in response to Paracoccidioides species

Memórias do Instituto Oswaldo Cruz ◽

10.1590/0074-02760200238 ◽

2020 ◽

Vol 115 ◽

Author(s):

Junya de Lacorte Singulani ◽

Julhiany de Fátima da Silva ◽

Fernanda Patricia Gullo ◽

Marina Célia Costa ◽

Ana Marisa Fusco-Almeida ◽

...

Keyword(s):

Fungal Host ◽

Host Interactions

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Computational Analysis Reveals a Key Regulator of Cryptococcal Virulence and Determinant of Host Response

mBio ◽

10.1128/mbio.00313-16 ◽

2016 ◽

Vol 7 (2) ◽

Cited By ~ 22

Author(s):

Stacey R. Gish ◽

Ezekiel J. Maier ◽

Brian C. Haynes ◽

Felipe H. Santiago-Tirado ◽

Deepa L. Srikanta ◽

...

Keyword(s):

Cryptococcus Neoformans ◽

Host Response ◽

Experimental Investigations ◽

Transcriptional Level ◽

Melanin Production ◽

Host Interactions ◽

Polysaccharide Capsule ◽

Genes Encoding ◽

Host Cell Interactions ◽

Opportunistic Fungal Pathogen

ABSTRACT Cryptococcus neoformans is a ubiquitous, opportunistic fungal pathogen that kills over 600,000 people annually. Here, we report integrated computational and experimental investigations of the role and mechanisms of transcriptional regulation in cryptococcal infection. Major cryptococcal virulence traits include melanin production and the development of a large polysaccharide capsule upon host entry; shed capsule polysaccharides also impair host defenses. We found that both transcription and translation are required for capsule growth and that Usv101 is a master regulator of pathogenesis, regulating melanin production, capsule growth, and capsule shedding. It does this by directly regulating genes encoding glycoactive enzymes and genes encoding three other transcription factors that are essential for capsule growth: GAT201 , RIM101 , and SP1 . Murine infection with cryptococci lacking Usv101 significantly alters the kinetics and pathogenesis of disease, with extended survival and, unexpectedly, death by pneumonia rather than meningitis. Our approaches and findings will inform studies of other pathogenic microbes. IMPORTANCE Cryptococcus neoformans causes fatal meningitis in immunocompromised individuals, mainly HIV positive, killing over 600,000 each year. A unique feature of this yeast, which makes it particularly virulent, is its polysaccharide capsule; this structure impedes host efforts to combat infection. Capsule size and structure respond to environmental conditions, such as those encountered in an infected host. We have combined computational and experimental tools to elucidate capsule regulation, which we show primarily occurs at the transcriptional level. We also demonstrate that loss of a novel transcription factor alters virulence factor expression and host cell interactions, changing the lethal condition from meningitis to pneumonia with an exacerbated host response. We further demonstrate the relevant targets of regulation and kinetically map key regulatory and host interactions. Our work elucidates mechanisms of capsule regulation, provides methods and resources to the research community, and demonstrates an altered pathogenic outcome that resembles some human conditions.

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