Diffusible component from the spore surface of the fungus Aspergillus fumigatus which inhibits the macrophage oxidative burst is distinct from gliotoxin and other hyphal toxins

Abstract

C, or aurasperone-C is not proved. The spore toxin may exert its effect through its Background -The fungus Aspergillus ability to diffuse rapidly into the lung lining fumigatus, whose spores are present fluid, diminish the macrophage oxidative ubiquitously in the air, causes a range of burst, and play a part in allowing A diseases in the human lung. A small mofumigatus to persist in the lung and manilecular weight (<10 kD) heat stable toxin fest its well known pathogenic effects. released from the spores of clinical and (Thorax 1997;52:796-801) environmental isolates of A fumigatus within minutes of deposition in aqueous Keywords: Aspergillus fumigatus, macrophage, gliotoxin, solution has previously been described. A fumagillin, helvolic acid, fumigaclavine-C, aurasperone-C. key effect of the toxin was to inhibit the oxidative burst of macrophages as measured by superoxide anion release. It was The fungus Aspergillus fumigatus is commonly hypothesised that the toxin was one of the found in the environment, its usual habitat commonly found A fumigatus hyphal tox-being dead or decaying organic matter. The ins such as gliotoxin. This inhibitor may fungus causes many human lung diseases 1 2 and be an important factor which allows the a major factor in determining the pathogenicity fungus to colonise the lung.of the fungus is the size of the spores (around Methods -The spore derived inhibitor was 3 m in diameter) which are present ubishown to inhibit the respiratory burst of quitously in the air. Mullins et al 3 have shown rat alveolar macrophages, as measured that many more spores of A fumigatus are presby the generation of superoxide anion. ent in the lungs at necropsy than would be Samples of the spore diffusate were subject anticipated from their presence in the air. The to reversed phase high performance spores therefore appear to have some survival liquid chromatography (HPLC), thin layer advantage in the human lung over other spores. chromatography (TLC), high perform-The survival rate of spores of A fumigatus in ance thin layer chromatography rabbit lung is greater than that of control spores (HPTLC), or organic extraction followed of a similar size. 4 Several factors have been by TLC or HPLC to identify the presence suggested as contributing to the pathogenesis of gliotoxin, fumagillin, helvolic acid, of A fumigatus. fumigaclavine-C, and aurasperone-C.Proteases, including a 32 kD chymotrypsinCommercially obtained preparations of like protease present on spores and hyphae, the toxins gliotoxin, fumagillin and hel-have been shown to reduce cell spreading 5 and volic acid and extracts enriched for promote detachment of cultured cells. 6 7 A low fumigaclavine-C and aurasperone-C were molecular weight component from the spore used as internal and external standards surface has been shown to inhibit the spreading and in the respiratory burst meas-and chemotaxis of macrophages, 5 to inhibit urements.the macrophage respiratory burst, 8 and also to Results -Gliotoxin, fumagillin, helvolic prevent phagocyt...

Early Neutrophil Recruitment and Aggregation in the Murine Lung Inhibit Germination ofAspergillus fumigatusConidia

“…There was also only 10% less conidial fluorescence in AM from C57BL/6 mice than in AM from gp91 phoxϪ/Ϫ mice. Together, these observations indicate that oxidants in AM either have a modest effect on conidia or that conidia may be inhibiting AM-derived oxidants (21). In contrast to the findings with PMN aggregates, the persistence of conidial fluorescence in AM from gp91 phoxϪ/Ϫ mice was not associated with increased germination of these conidia, and germination rates overall were very low for conidia in AM from BALB/c and C57BL/6 mice as well as gp91…”

Galleria mellonellaas a host model to studyAspergillus terreusvirulence and amphotericin B resistance

“…[27][28][29][30][31] Additionally, fumagillin is also produced by A. fumigatus during hyphal growth and has been identified as an inhibitor of angiogenesis through a covalent interaction with methionine aminopeptidase-2 and suppresses tumor growth. 32,33 The production of gliotoxin and fumagillin was also proved in infected G. mellonella larvae. 31,34 A study by Lewis et al 35 detected gliotoxin in culture medium of A. terreus, but as we did not test gliotoxin production, or any other secondary metabolites, of the 5 different isolates we can only speculate its contribution to differences in virulence potential.…”

Nonribosomal cyclic peptides: specific markers of fungal infections

“…were shown to facilitate fungus penetration into the host tissue. 24 Interestingly, low-molecular-weight proteins have also been described for Emericela nidulans and Aspergillus niger. 25 However, no specific fungal protein marker molecule has been found.…”