Fungal pathogens such as Aspergillus fumigatus have a very complex life cycle, allowing the generation of asexual spores (conidia) that help the pathogen to spread in the air and be inhaled by hosts. In healthy hosts, they will be eliminated by the immune system; but in immunocompromised hosts, they lead to a fatal disease, pulmonary aspergillosis. In a work published in the journal PNAS, Antoine Loquet's group in collaboration with the team of Vishukumar Aimanianda at the Institut Pasteur have developed a new approach using solid-state NMR spectroscopy to determine the evolution of the cell wall of these spores at the atomic scale during their germination.

 

Understanding the atomic scale molecular organization of a pathogen's cell wall remains a technical challenge, as it consists of numerous biomolecules such as sugars, proteins, pigments and lipids, which are often difficult to identify and quantify. Many modern analytical approaches to study these cell walls are destructive, as they require selective extraction of the constituent biomolecules using chemical, biochemical or enzymatic treatments. However, these approaches remain limited to study the evolution of the pathogen during its life cycle and to compare the different morphologies it can adopt. Researchers from the CBMN and the IECB, in collaboration with the Institut Pasteur have developed a new method based on solid-state nuclear magnetic resonance spectroscopy (NMR) to understand the molecular organization of fungal spores of the pathogen Aspergillus fumigatus during germination. This research benefited from access to the national platform Infranalytics (CNRS FR2054).

 

Researchers used solid-state NMR techniques to compare the composition and abundance of polysaccharides such as glucans and chitins at three different morphological stages during the germination of A. fumigatus. Methods exploiting magic-angle spinnin highlighted the role of the sugar called galactosaminogalactan, synthesized during germination, as well as the detection of mobile triglycerides. By combining solid-state NMR data allowing the identification and quantification of sugars with surface accessibility measurements, molecular organization models of different morphotypes of A. fumigatus were proposed. This new solid-state NMR methodology is currently being tested by the researchers on other fungal pathogens in order to compare the structure of their cell walls. The action of antifungal compounds on their surface organization could also be studied by this method.

Reference:

Solid-state NMR molecular snapshots of Aspergillus fumigatus cell wall architecture during a conidial morphotype transition

Gaëlle Lamon, Alons Lends, Isabel Valsecchi, Sarah Sze Wah Wong, Vincent Duprès, Frank Lafont, James Tolchard, Christine Schmitt, Adeline Mallet, Axelle Grélard, Estelle Morvan, Erick J. Dufourc, Birgit Habenstein, J. Iñaki Guijarro, Vishukumar Aimanianda, Antoine Loquet

Proc Natl Acad Sci U S A., 2023, January 31, 120 (6) e2212003120