# Cell wall arabinogalactan is responsible for Fungitell cross reactivity in nocardiosis

## TL;DR

This study identifies a bacterial cell wall component causing false positive fungal tests in nocardiosis patients, offering a path to better diagnostics.

## Contribution

The study reveals nocardial arabinogalactan as the cause of Fungitell cross-reactivity and its structural basis.

## Key findings

- Nocardial cell wall arabinogalactan causes Fungitell cross-reactivity when released in vivo.
- The reactivity is due to a β-glucose substitution in the galactan domain unique to Nocardia.
- The optimal antigen is a tetramer of the trisaccharide repeating unit in arabinogalactan.

## Abstract

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.