Cell wall arabinogalactan is responsible for Fungitell cross reactivity in nocardiosis

Area of Science:

• Microbiology
• Immunology
• Medical Diagnostics

Background:

• Nocardiosis is a severe infection in immunocompromised individuals, particularly transplant recipients.
• Diagnosis is challenging due to slow bacterial growth and varied symptoms, leading to delayed treatment and high mortality.
• A significant diagnostic issue is the cross-reactivity of some nocardiosis patients with fungal diagnostics like the Fungitell assay, which detects (1,3)-β-D-glucan.

Purpose of the Study:

• To elucidate the molecular basis of cross-reactivity between Nocardia infections and the (1,3)-β-D-glucan assay.
• To identify the specific Nocardia antigen responsible for this diagnostic interference.
• To provide structural insights for developing more specific diagnostic methods for nocardiosis.

Main Methods:

• Analysis of Nocardia cell wall components, specifically arabinogalactan.
• Structural characterization of the antigen involved in cross-reactivity.
• Investigation of the role of β-glucose substitution in the galactan domain.
• Determination of the optimal antigenic structure (tetramer of trisaccharide repeating unit).

Main Results:

• Nocardial cell wall arabinogalactan acts as a cryptic antigen that is exposed upon bacterial lysis in vivo.
• The cross-reactivity is attributed to a unique β-glucose substitution of the galactan domain, specific to Nocardia species.
• A tetramer of the trisaccharide repeating unit was identified as the optimal antigen responsible for the observed reactivity.

Conclusions:

• Structural evidence confirms that Nocardia arabinogalactan is responsible for Fungitell assay cross-reactivity.
• This finding explains the false-positive results in fungal diagnostics for some nocardiosis patients.
• The study lays the groundwork for developing novel, specific diagnostic tools for Nocardia infections.