Conidia of Aspergillus fumigatus are inhaled by humans on daily basis. As a consequence, these conidia can cause infections that differ in severity ranging from allergic bronchopulmonary... Show moreConidia of Aspergillus fumigatus are inhaled by humans on daily basis. As a consequence, these conidia can cause infections that differ in severity ranging from allergic bronchopulmonary aspergillosis to invasive aspergillosis. In this study we compared virulence of five A. fumigatus isolates in four different infection models to address the predictive value of different model systems. Two of the A. fumigatus strains were isolated from dogs with a non-invasive sino-nasal aspergillosis (DTO271-B5 and DTO303-F3), while three strains were isolated from human patients with invasive aspergillosis (Af293, ATCC46645 and CEA10). Infection models used encompassed cultured type II A549 lung epithelial cells, Protostelium aurantium amoeba, Galleria melonella larvae and zebrafish embryos. No major differences in virulence between these five strains were observed in the lung epithelial cell model. In contrast, strain ATCC46645 was most virulent in the amoeba and zebrafish model, whereas it was much less virulent in the Galleria infection model. DTO303-F3 was most virulent in the latter model. In general, reference strain Af293 was less virulent as compared to the other strains. Genome sequence analysis showed that this latter strain differed from the other four strains in 136 SNPs in virulence-related genes. Together, our results show that virulence of individual A. fumigatus strains show significant differences between infection models. We conclude that the predictive value of different model systems varies since the relative virulence across fungal strains does not hold up across different infection model systems. Show less
Claessen, D.; Rink, R.; Jong, W. de; Siebring, J.; Vreugd, P. de; Boersma, F.G.H.; ... ; Wosten, H.A.B. 2003
Streptomycetes exhibit a complex morphological differentiation. After a submerged mycelium has been formed, filaments grow into the air to septate into spores. A class of eight hydrophobic secreted... Show moreStreptomycetes exhibit a complex morphological differentiation. After a submerged mycelium has been formed, filaments grow into the air to septate into spores. A class of eight hydrophobic secreted proteins, ChpA–H, was shown to be instrumental in the development of Streptomyces coelicolor. Mature forms of ChpD–H are up to 63 amino acids in length, and those of ChpA–C are larger (±225 amino acids). ChpA–C contain two domains similar to ChpD–H, as well as a cell-wall sorting signal. The chp genes were expressed in submerged mycelium (chpE and chpH) as well as in aerial hyphae (chpA–H). Formation of aerial hyphae was strongly affected in a strain in which six chp genes were deleted (ΔchpABCDEH). A mixture of ChpD–H purified from cell walls of aerial hyphae complemented the ΔchpABCDEH strain extracellularly, and it accelerated development in the wild-type strain. The protein mixture was highly surface active, and it self-assembled into amyloid-like fibrils at the water–air interface. The fibrils resembled those of a surface layer of aerial hyphae. We thus conclude that the amyloid-like fibrils of ChpD–H lower the water surface tension to allow aerial growth and cover aerial structures, rendering them hydrophobic. ChpA–C possibly bind ChpD–H to the cell wall. Show less
