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Updated: Jul 25, 2026
Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
Published on: March 9, 2018
Purification and characterization of factors produced by Aspergillus fumigatus which affect human ciliated
R Amitani1, G Taylor, E N Elezis
1Department of Thoracic Medicine, Royal Brompton National Heart and Lung Institute, London, United Kingdom.
Abstract:
The mechanisms by which Aspergillus fumigatus colonizes the respiratory mucosa are unknown. Culture filtrates of eight of nine clinical isolates of A. fumigatus slowed ciliary beat frequency and damaged human respiratory epithelium in vitro. These changes appeared to occur concurrently. Culture filtrates of two clinical isolates of Candida albicans had no effect on ciliated epithelium. We have purified and characterized cilioinhibitory factors of a clinical isolate of A. fumigatus. The cilioinhibitory activity was heat labile, reduced by dialysis, and partially extractable into chloroform. The activity was associated with both high- and low-molecular-weight factors, as determined by gel filtration on Sephadex G-50. A low-molecular-weight cilioinhibitory factor was further purified by reverse-phase high-performance liquid chromatography and shown by mass spectrometry to be gliotoxin, a known metabolite of A. fumigatus. Gliotoxin significantly slowed ciliary beat frequency in association with epithelial damage at concentrations above 0.2 microgram/ml; other Aspergillus toxins, i.e., fumagillin and helvolic acid, were also cilioinhibitory but at much higher concentrations. High-molecular-weight (> or = 35,000 and 25,000) cilioinhibitory materials had neither elastolytic nor proteolytic activity and remain to be identified. Thus, A. fumigatus produces a number of biologically active substances which slow ciliary beating and damage epithelium and which may influence colonization of the airways.
Insights
Aspergillus fumigatus culture filtrates impair respiratory cilia and epithelium. The toxin gliotoxin significantly slows ciliary beat frequency and damages cells, potentially aiding airway colonization.
Area of Science:
- Microbiology
- Pulmonology
- Toxicology
Background:
- The mechanisms of Aspergillus fumigatus airway colonization are not well understood.
- A. fumigatus is an opportunistic pathogen that can cause invasive disease in immunocompromised individuals.
- Respiratory mucosa and ciliary function are critical for clearing inhaled pathogens.
Purpose of the Study:
- To investigate the effects of A. fumigatus on human respiratory epithelium and cilia.
- To identify and characterize the factors produced by A. fumigatus responsible for ciliary dysfunction and epithelial damage.
Main Methods:
- In vitro exposure of human respiratory epithelial cells to culture filtrates of A. fumigatus and Candida albicans.
- Purification and characterization of cilioinhibitory factors using gel filtration, reverse-phase HPLC, and mass spectrometry.
- Assessment of ciliary beat frequency and epithelial integrity.
Main Results:
- A. fumigatus culture filtrates significantly reduced ciliary beat frequency and damaged respiratory epithelium in vitro.
- Gliotoxin, a low-molecular-weight A. fumigatus metabolite, was identified as a potent cilioinhibitory factor causing epithelial damage at concentrations above 0.2 microgram/ml.
- Other Aspergillus toxins, fumagillin and helvolic acid, also exhibited cilioinhibitory activity but at higher concentrations.
- High-molecular-weight factors with cilioinhibitory activity were detected but not identified.
Conclusions:
- A. fumigatus produces multiple biologically active substances, including gliotoxin, that impair ciliary function and damage respiratory epithelium.
- These factors may play a significant role in the colonization of the airways by A. fumigatus.
- Further research is needed to identify the high-molecular-weight cilioinhibitory factors.
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