Vaccination with Live or Heat-Killed Aspergillus fumigatus Δ <i>sglA</i> Conidia Fully Protects Immunocompromised Mice from Invasive Aspergillosis

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ABSTRACT

Aspergillus fumigatus causes invasive aspergillosis (IA) in immunocompromised patients, resulting in high mortality rates. Currently, no vaccine formulations to promote immune protection in at-risk individuals have been developed. In this work, we deleted the sterylglucosidase-encoding gene, sglA, in Aspergillus fumigatus and investigated its role in fungal virulence and host vaccine protection. The Δ sglA mutant accumulated sterylglucosides (SGs), newly studied immunomodulatory glycolipids, and exhibited reduced hyphal growth and altered compositions of cell wall polysaccharides. Interestingly, the Δ sglA mutant was avirulent in two murine models of IA and was fully eliminated from the lungs. Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed Δ sglA conidia were fully protected against a lethal wild-type A. fumigatus challenge. These results highlight the potential of SG-accumulating strains as safe and promising vaccine formulations against invasive fungal infections.

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Most cited references 60

Record: found
Abstract: not found
Article: not found

A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION

E G BLIGH, W. Dyer (1959)

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Record: found
Abstract: found
Article: not found

Hidden killers: human fungal infections.

Gordon Brown, David W. Denning, Neil Gow … (2012)

Although fungal infections contribute substantially to human morbidity and mortality, the impact of these diseases on human health is not widely appreciated. Moreover, despite the urgent need for efficient diagnostic tests and safe and effective new drugs and vaccines, research into the pathophysiology of human fungal infections lags behind that of diseases caused by other pathogens. In this Review, we highlight the importance of fungi as human pathogens and discuss the challenges we face in combating the devastating invasive infections caused by these microorganisms, in particular in immunocompromised individuals.

0 comments Cited 822 times – based on 0 reviews      Review now

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Record: found
Abstract: found
Article: not found

Aspergillus fumigatus and aspergillosis.

J P Latgé (1999)

Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Humans and animals constantly inhale numerous conidia of this fungus. The conidia are normally eliminated in the immunocompetent host by innate immune mechanisms, and aspergilloma and allergic bronchopulmonary aspergillosis, uncommon clinical syndromes, are the only infections observed in such hosts. Thus, A. fumigatus was considered for years to be a weak pathogen. With increases in the number of immunosuppressed patients, however, there has been a dramatic increase in severe and usually fatal invasive aspergillosis, now the most common mold infection worldwide. In this review, the focus is on the biology of A. fumigatus and the diseases it causes. Included are discussions of (i) genomic and molecular characterization of the organism, (ii) clinical and laboratory methods available for the diagnosis of aspergillosis in immunocompetent and immunocompromised hosts, (iii) identification of host and fungal factors that play a role in the establishment of the fungus in vivo, and (iv) problems associated with antifungal therapy.

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Author and article information

Contributors

Maurizio Del Poeta:

ORCID: https://orcid.org/0000-0001-8418-3120

Luis R. Martinez: Role: Editor

Journal

Journal ID (nlm-ta): mBio

Journal ID (iso-abbrev): mBio

Journal ID (publisher-id): mbio

Title: mBio

Publisher: American Society for Microbiology (1752 N St., N.W., Washington, DC )

ISSN (Electronic): 2150-7511

Publication date (Electronic, pub): 6 September 2022

Publication date (Electronic, collection): Sep-Oct 2022

Publication date PMC-release: 6 September 2022

Volume: 13

Issue: 5

Electronic Location Identifier: e02328-22

Affiliations

[a ] Department of Microbiology and Immunology, Stony Brook Universitygrid.36425.36, , Stony Brook, New York, USA

[b ] Departamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, Brazil

[c ] Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

[d ] Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

[e ] Division of Infectious Diseases, School of Medicine, Stony Brook Universitygrid.36425.36, , Stony Brook, New York, USA

[f ] Veterans Administration Medical Center, Northport, New York, USA

University of Florida

Author notes

Caroline Mota Fernandes and Tyler G. Normile are co-first authors who contributed equally to this work. The order of names was decided as Caroline Mota Fernandes constructed and characterized the strain and Tyler G. Normile performed the in vivo work.

The authors declare a conflict of interest. Maurizio Del Poeta, M.D., is a Co-Founder and the Chief Scientific Officer (CSO) of MicroRid Technologies Inc. All other authors have no conflicts of interest.

Author information

Leonardo Nimrichter https://orcid.org/0000-0001-9281-6856

Iran Malavazi https://orcid.org/0000-0002-4526-4961

Maurizio Del Poeta https://orcid.org/0000-0001-8418-3120

Article

Publisher ID: 02328-22 Publisher ID: mbio.02328-22

DOI: 10.1128/mbio.02328-22

PMC ID: 9600187

PubMed ID: 36066100

SO-VID: 167d8348-688d-44d8-9d10-c352a09f42c3

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

History

Date received : 17 August 2022

Date accepted : 17 August 2022

Page count

supplementary-material: 7, Figures: 6, Tables: 0, Equations: 0, References: 60, Pages: 19, Words: 12081

Funding

Funded by: HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID), FundRef https://doi.org/10.13039/100000060;

Award ID: AI136934