Effect of ostreolysin, an Asp-hemolysin isoform, on human chondrocytes and osteoblasts, and possible role of Asp-hemolysin in pathogenesis

Abstract

Aspergillus fumigatus, a pathogenic mould causing a wide range of diseases including aspergillosis, produces a series of toxic substances which appear to act in an additive and/or synergic way on cells. Aspergillosis generally occurs in immunocompromised hosts or is associated with organ transplantation. From the muscul skeleton system the vertebrae, ribs and orbit are the most commonly affected, while the joints are less frequent targets. The cytolytic protein Asp-hemolysin is one of the toxins produced by Aspergillus fumigatus during infection. It belongs to the aegerolysin protein family and shares 43% identity in amino acid sequence with ostreolysin, a cytolysin from the mushroom Pleurotus ostreatus. In this work, ostreolysin was used in an experimental model to study the in vitro effects of aegerolysin-like proteins on human chondrocytes and osteoblasts. Immunostaining analyses showed selective binding and clustering of the protein on chondrocyte membranes, pointing to its association with distinctive membrane microdomains. Consequently, ostreolysin can induce effective permeabilization of both chondrocytes and osteoblasts. Based on sequence similarities of ostreolysin and Asp-hemolysin, their comparable cytolytic effects towards different cells, and similar signs of intoxication in experimental animals, our results indicate that Asp-hemolysin might be considered as a possible virulence factor of Aspergillus fumigatus during the infection of bone and cartilage.