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Distinct proteomes and allergen profiles appear across the life-cycle stages of Alternaria alternata - 05/08/24

Doi : 10.1016/j.jaci.2024.03.026 
Michael Brad Strader, PhD a, , Aishwarya L. Saha, BS a, Chantal Fernandes, PhD b, Kavita Sharma, PhD a, Christian Hadiwinarta, MSc a, Daniela Calheiros, MSc b, Gonçalo Conde-de-Oliveira, MSc b, Teresa Gonçalves, PhD b, Jay E. Slater, MD a
a Laboratory of Immunobiochemistry, Division of Bacterial, Parasitic and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Md 
b University of Coimbra, CNC-UC – Center for Neuroscience and Cell Biology, FMUC – Faculty of Medicine of the University of Coimbra, Coimbra, Portugal 

Corresponding author: Michael Brad Strader, PhD, Laboratory of Immunobiochemistry, Division of Bacterial, Parasitic and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD 20993.Laboratory of ImmunobiochemistryDivision of BacterialParasitic and Allergenic ProductsOffice of Vaccines Research and ReviewCenter for Biologics Evaluation and ResearchU.S. Food and Drug Administration10903 New Hampshire AveSilver SpringMD20993

Abstract

Background

Alternaria alternata is associated with allergic respiratory diseases, which can be managed with allergen extract–based diagnostics and immunotherapy. It is not known how spores and hyphae contribute to allergen content. Commercial allergen extracts are manufactured by extracting proteins without separating the different forms of the fungus.

Objective

We sought to determine differences between spore and hyphae proteomes and how allergens are distributed in A alternata.

Methods

Data-independent acquisition mass spectrometry was used to quantitatively compare the proteomes of asexual spores (nongerminating and germinating) with vegetative hyphae.

Results

We identified 4515 proteins in nongerminating spores, germinating spores, and hyphae; most known allergens are more abundant in nongerminating spores. On comparing significant protein fold-change differences between nongerminating spores and hyphae, we found that 174 proteins were upregulated in nongerminating spores and 80 proteins in hyphae. Among the spore proteins are ones functionally involved in cell wall synthesis, responding to cellular stress, and maintaining redox balance and homeostasis. On comparing nongerminating and germinating spores, 25 proteins were found to be upregulated in nongerminating spores and 54 in germinating spores. Among the proteins specific to germinating spores were proteases known to be virulence factors. One of the most abundant proteins in the spore proteome is sialidase, which has not been identified as an allergen but may be important in the pathogenicity of this fungus. Major allergen Alt a 1 is present at low levels in spores and hyphae and appears to be largely secreted into growth media.

Conclusions

Spores and hyphae express overlapping but distinct proteomes. Most known allergens are found more abundantly in nongerminating spores.

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Key words : Allergen extracts, Alternaria, mold, proteome, allergens

Abbreviations used : DIA, MM


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© 2024  Publicado por Elsevier Masson SAS.
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Vol 154 - N° 2

P. 424-434 - août 2024 Regresar al número
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