# Using Solid-State NMR Spectroscopy to Elucidate Cell Wall Structural Dynamics Involved in Virulence and Drug Response of Aspergillus fumigatus

> **NIH NIH R21** · LOUISIANA STATE UNIV A&M COL BATON ROUGE · 2020 · $217,464

## Abstract

Project Summary
 The goal of the proposed research is to identify the structural characteristics of fungal cell walls involved in
virulence and drug response. Invasive fungal infection results in fatal diseases in individuals with
immunodeficiency. Existing antifungal drugs have been mainly designed to target fungal cell membranes, but
they also bind to human cell membranes, thus causing severe side effects. Recent efforts have been devoted to
developing agents that bind fungal cell walls because they contain carbohydrates, for example, chitins and β-
glucans, that are absent in human. Such biomolecules, however, evade high-resolution structural
characterization as they are typically insoluble and polymorphic in structure. Recently, we initiated a project to
investigate the native cell wall structure of Aspergillus fumigatus, a major pathogenic fungus causing invasive
aspergillosis, using solid-state NMR spectroscopy. This method provides atomic-level insight into the
supramolecular assembly of carbohydrates and proteins in native fungal cell walls with minimal perturbation.
The central hypothesis is that the large-scale spatial rearrangement of biomolecules directly regulates fungal
virulence and drug resistance. This hypothesis will be tested by pursuing two specific aims: 1) identify the
structural variation of cell walls from pathogenic and non-pathogenic fungi, and between the young and aged
fungi; 2) elucidate the molecular effects of antifungal drugs on the cell wall structure of wildtype and drug-resistant
strains. The expected outcomes include the first set of comparative models of Aspergillus cell wall structure with
dependence on four variables: fungal type and pathogenicity, age, drug concentration, and genetic mutants. The
approaches established in this project will be widely applicable to investigations of many other fungal pathogens.
This combined effort of biophysical methods, carbohydrate chemistry, and medical mycology presents a unique
and novel contribution as it bridges the gap between molecular structures with phenotype and drug effects. The
dynamic and comprehensive view of the functional structure of fungal cell wall obtained here, in the long term,
will facilitate the discovery and evaluation of novel therapies that can effectively inhibit a broad spectrum of
pathogenic fungi by targeting their cell wall structure or biosynthesis.

## Key facts

- **NIH application ID:** 9876497
- **Project number:** 1R21AI149289-01
- **Recipient organization:** LOUISIANA STATE UNIV A&M COL BATON ROUGE
- **Principal Investigator:** PING WANG
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $217,464
- **Award type:** 1
- **Project period:** 2020-02-05 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876497

## Citation

> US National Institutes of Health, RePORTER application 9876497, Using Solid-State NMR Spectroscopy to Elucidate Cell Wall Structural Dynamics Involved in Virulence and Drug Response of Aspergillus fumigatus (1R21AI149289-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9876497. Licensed CC0.

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