Document Type

Article

Peer Reviewed

1

Publication Date

1-1-2015

NLM Title Abbreviation

PLoS One

Journal/Book/Conference Title

PLoS One

PubMed ID

25723175

DOI of Published Version

10.1371/journal.pone.0117336

Total Pages

14

Abstract

Aspergillus fumigatus is an environmental mold that causes severe, often fatal invasive infections in immunocompromised patients. The search for new antifungal drug targets is critical, and the synthesis of the cell wall represents a potential area to find such a target. Embedded within the main β-1,3-glucan core of the A. fumigatus cell wall is a mixed linkage, β-D-(1,3;1,4)-glucan. The role of this molecule or how it is synthesized is unknown, though it comprises 10% of the glucans within the wall. While this is not a well-studied molecule in fungi, it has been studied in plants. Using the sequences of two plant mixed linkage glucan synthases, a single ortholog was identified in A. fumigatus (Tft1). A strain lacking this enzyme (tft1Δ) was generated along with revertant strains containing the native gene under the control of either the native or a strongly expressing promoter. Immunofluorescence staining with an antibody against β-(1,3;1,4)-glucan and biochemical quantification of this polysaccharide in the tft1Δ strain demonstrated complete loss of this molecule. Reintroduction of the gene into the knockout strain yielded reappearance in amounts that correlated with expected expression of the gene. The loss of Tft1 and mixed linkage glucan yielded no in vitro growth phenotype. However, there was a modest increase in virulence for the tft1Δ strain in a wax worm model. While the precise roles for β-(1,3;1,4)-glucan within A. fumigatus cell wall are still uncertain, it is clear that Tft1 plays a pivotal role in the biosynthesis of this cell wall polysaccharide.

Keywords

OAfund

Journal Article Version

Version of Record

Published Article/Book Citation

PLoS ONE 10(2): e0117336. doi:10.1371/journal.pone.0117336

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons 1.0 Public Domain Dedication.

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Pathology Commons

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URL

https://ir.uiowa.edu/pathology_pubs/3