Cell wall arabinogalactan is responsible for Fungitell cross reactivity in nocardiosis
Nocardiosis is a serious infection in immunosuppressed patients, especially transplant recipients. The slow-growing phenotype of the bacterium and the variety of symptoms complicate diagnosis and delay antimicrobial therapy, resulting in high mortality rates despite effective treatments. A further complication is that some nocardiosis patients test positive in fungal diagnostics that detect (1,3)-β-D-glucan (the Fungitell assay), but the basis for this cross-reactivity remains unknown. We demonstrate that nocardial cell wall arabinogalactan is a cryptic antigen responsible for cross-reactivity in the Fungitell assay and that this antigen is revealed in vivo following bacterial cell lysis. We further show that the reactivity results from a β-glucose substitution of the galactan domain, a modification specific to nocardia, and identify the optimal antigen as a tetramer of the trisaccharide repeating unit. By providing structural evidence for Fungitell cross-reactivity during nocardiosis, this work paves the way for developing specific diagnostic tools that are currently lacking.
Authors
- Frédéric Wallet (ORCID: https://orcid.org/0000-0002-2368-5466)
- Todd L. Lowary (ORCID: https://orcid.org/0000-0002-8331-8211)
- Yann Guérardel (ORCID: https://orcid.org/0000-0003-4967-9512)
- Marie Frimat (ORCID: https://orcid.org/0000-0002-7461-8298)
- Wei‐Ting Chang (ORCID: https://orcid.org/0009-0001-5568-2120)
- Séverine Loridant (ORCID: https://orcid.org/0000-0002-9440-7869)
- Marc Hazzan (ORCID: https://orcid.org/0000-0002-9863-8840)
- Daniel Poulain (ORCID: https://orcid.org/0000-0002-0729-5468)
- Christophe Mariller (ORCID: https://orcid.org/0000-0002-1881-0971)
- Marie Titécat (ORCID: https://orcid.org/0000-0002-5860-0936)
- Karine Faure (ORCID: https://orcid.org/0000-0002-2608-9790)
- Boualem Sendid (ORCID: https://orcid.org/0000-0003-1577-7325)
- Pascal Letowski
- Marc Ulrich
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université de Lille (FR)
- Institut Pasteur de Lille (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Lille’s Cardiology Hospital (FR)
- Institute of Biological Chemistry, Academia Sinica (TW)
- Unité de Glycobiologie Structurale et Fonctionnelle (FR)
- Lille Inflammation Research International Center (FR)
- Groupe Hospitalier de l'Institut Catholique de Lille (FR)
Publication Details
- Journal
- Journal of Biological Chemistry
- Published
- 2025-11-05
- DOI
- https://doi.org/10.1016/j.jbc.2025.110900
- Primary Topic
- Actinomycetales infections and treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Institut National de la Santé et de la Recherche Médicale
- Academia Sinica