Asp-hemolysin Significance as a Virulence Factor with Biological Activities from Aspergillus fumigatus.

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  • Ａｓｐｅｒｇｉｌｌｕｓ　ｆｕｍｉｇａｔｕｓ由来のＡｓｐ‐ｈｅｍｏｌｙｓｉｎの生理活性と病原性因子としての意義

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Abstract

Asp-hemolysin from Aspergillus fumigatus (A. fumigatus) Fresenius-Muramatsu is a heat-labile protein toxin, which causes lysis of a wide range of erythrocyte species in vitro. The mature Asp-hemolysin consists of 126 amino acid residues, which is deduced from the nucleotide sequence of Asp-hemolysin cDNA and the N-terminal amino acid sequence of purified Asp-hemolysin. The relationship between the biological activities of Asp-hemolysin and the infection of A. fumigatus in mice was examined. With simultaneous inoculation of viable spores and Asp-hemolysin in mice, Asp-hemolysin showed a tendency to help the realization and expansion of infection. Actually, the secretion of Asp-hemolysin from mycelia in the foci of infection was immunohistochemically observed in the kidney and brain. In histopathological aspects, necrotic lesions of various degrees were observed in the heart and liver of mice inoculated with Asp-hemolysin, and the toxin was definitely bound to arterial walls in the kidney and brain. Asp-hemolysin showed high cytotoxicity to human leukocytes and guinea pig peritoneal macrophages in vitro. We also found that, depending on the levels of protein or mRNA, several clinical isolates of A. fumigatus also produce Asp-hemolysin. Our results indicate that Asp-hemolysin with multiple biological functions may play an important role as a virulence factor in the pathogenesis of infection by A. fumigatus.

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